Association between Prior Cytomegalovirus Infection and the Risk of Restenosis after Coronary Atherectomy
Yi Fu Zhou, M.D., Martin B. Leon, M.D., Myron A. Waclawiw, Ph.D., Jeffery J. Popma, M.D., Zu Xi Yu, M.D., Toren Finkel, M.D., Ph.D., and Stephen E. Epstein, M.D.
Background Restenosis occurs commonly after coronary angioplastyand atherectomy, but the causes of restenosis are poorly understood.Recently, it has been found that cytomegalovirus (CMV) DNA ispresent in restenotic lesions from atherectomy specimens. Thisand other evidence suggest that CMV may have a role in the processof restenosis.
Methods We prospectively studied 75 consecutive patients undergoingdirectional coronary atherectomy for symptomatic coronary arterydisease. Before atherectomy was performed, we measured bloodlevels of anti-CMV IgG antibodies to determine whether previousexposure to CMV increased the risk of restenosis, as determinedby coronary angiography performed six months after atherectomy.
Results After atherectomy, the mean (±SD) minimal luminaldiameter of the target vessel was greater in the 49 patientswho were seropositive for CMV than in the 26 patients who wereseronegative (3.18±0.51 mm vs. 2.89±0.45 mm, P= 0.01). After six months, however, the seropositive patientshad a greater reduction in the luminal diameter (1.24±0.83mm vs. 0.68±0.69 mm, P = 0.003), resulting in a significantlyhigher rate of restenosis in the seropositive patients (43 percentvs. 8 percent, P = 0.002). In a multivariable logistic-regressionmodel, CMV seropositivity and the CMV titer were independentlypredictive of restenosis (odds ratios, 12.9 and 8.1, respectively).There was no evidence of acute infection, since the titer ofanti-CMV IgG antibodies did not increase over time and testsfor anti-CMV IgM antibodies were negative in all patients.
Conclusions Prior infection with CMV is a strong independentrisk factor for restenosis after coronary atherectomy. If confirmed,these findings may help identify patients at risk for restenosis.
Neointimal hyperplasia and arterial remodeling cause restenosisin 20 to 50 percent of patients who have undergone coronaryangioplasty.1,2 Although the mechanisms are unknown, previousfindings have raised the possibility that cytomegalovirus (CMV)contributes to the development of restenosis in some patients.3In approximately one third of patients with restenosis, thelesions contain CMV DNA sequences. Smooth-muscle cells grownfrom such lesions express IE84, one of the virus's immediateearly proteins, and IE84 binds to and inhibits the p53 tumor-suppressorgene product. These effects may enhance the proliferation ofsmooth-muscle cells or inhibit apoptosis, either of which maycontribute to restenosis.3
CMV infection in immunocompetent adults is common4 and usuallyasymptomatic.5,6 Like other herpesviruses, CMV persists indefinitelyin certain host cells.7,8 Under certain circumstances (suchas immunosuppression due to the acquired immunodeficiency syndrome9or treatment after organ transplantation10), the virus can bereactivated and cause serious disease. In these situations,viral replication contributes to the disease process. However,there is evidence that CMV can also contribute to the diseaseprocess during an abortive infection,11 which is characterizedby viral-gene expression limited to immediate early gene productswithout viral replication. CMV immediate early gene products,for example, are known to affect the expression of many humancellular genes involved in inflammation and immunologic responses,12and as previously documented, CMV is present in smooth-musclecells from restenotic lesions and can express immediate earlygene products, which inhibit the p53 function.3 We thereforehypothesized that latent CMV may be reactivated locally in responseto vascular injury in a subgroup of patients undergoing coronaryangioplasty. By inhibiting the capacity of p53 either to blockthe progression of the cell cycle or to initiate apoptosis,as well as by other mechanisms, the virus may enhance the accumulationof smooth-muscle cells and thereby facilitate the developmentof restenosis. We conducted a prospective investigation to testthis hypothesis.
Methods
The patients in our study were part of the Optimal AtherectomyRestenosis Study (OARS), which was designed to determine thefrequency of restenosis after directional coronary atherectomy.A follow-up angiographic evaluation was performed approximatelysix months after the surgery. Our patients were from WashingtonHospital Center, Washington, D.C., which was one of four centersparticipating in OARS and which recruited 100 of its 211 patients.Of these 100 patients, 75 were enrolled in our study; 7 patientswere not enrolled because of an initial procedural complicationor a protocol violation, and 18 patients did not undergo follow-upangiography.
Before and six months after surgery, blood samples were collectedfor assays of anti-CMV IgG and IgM antibodies. The assays wereperformed without knowledge of the angiographic findings.
A patient was considered to have diabetes if he or she was takinginsulin or oral hypoglycemic agents or had previously receivedsuch treatment and was currently using dietary modificationto control the condition. A patient was considered to have hypertensionif he or she had received the diagnosis or was being treatedwith antihypertensive medications or dietary modification. Apatient was considered to have hypercholesterolemia if he orshe had a serum cholesterol value higher than 240 mg per deciliter(6.2 mmol per liter) at the time of angioplasty or was receivingcholesterol-lowering treatment.
Directional Atherectomy
Optimal directional coronary atherectomy consists of local plaqueresection followed by circumferential plaque resection withthe use of larger devices or higher balloon pressures and usuallyconcludes with adjunctive low-pressure balloon dilation. Ultrasonographicguidance is used to optimize the results. Of the 75 patientsin the study, 65 (87 percent) had adjunctive percutaneous transluminalcoronary angioplasty, resulting in a mean additional 10 percentreduction in the degree of stenosis. Stents were placed in twopatients (3 percent) after the atherectomy, because of severelumen-compromising dissections.
Angiographic Analysis
Cineangiograms were forwarded to the central angiographic laboratoryand were evaluated without knowledge of whether the patientswere seropositive or seronegative for anti-CMV antibodies. Base-line,postsurgical, and follow-up (six-month) cineangiograms wereanalyzed with an automated edge-detection algorithm (CardiovascularMeasurement System, Medis Medical Imaging Systems, Nuenen, theNetherlands). The minimal luminal diameter, interpolated referencediameter, and percentage of stenosis before and after atherectomyand at six months were measured from two projections; the averageof these two values is reported. An early gain in the diameterof the target vessel was defined as the minimal luminal diameterimmediately after surgery minus the minimal luminal diameterbefore surgery. A late loss in the luminal diameter was definedas the minimal luminal diameter immediately after surgery minusthe minimal luminal diameter at six months. The loss index wasdefined as the late loss divided by the early gain, expressedas a percentage. Restenosis was defined as more than 50 percentstenosis at follow-up in a vessel with less than 50 percentstenosis immediately after atherectomy.
Assays for CMV Antibodies
Tests for anti-CMV IgG antibodies were performed with an enzyme-linkedimmunosorbent assay (ELISA) kit (Cytomegelisa II, BioWhittaker,Walkersville, Md.), according to the manufacturer's directions.Antibody titers were determined on the basis of a standard curve.The threshold value was determined prospectively: an ELISA valueof less than 0.25 unit was considered a negative result, anda value of 0.25 unit or higher was considered a positive result,indicating prior exposure to CMV.
Tests for anti-CMV IgM antibodies were performed with an enzyme-linkedantibody-capture assay kit (CMV CAP-M, BioWhittaker), accordingto the manufacturer's directions. An index value of less than0.9 was interpreted as a negative result, and a value of morethan 1.1 was interpreted as a positive result; values between0.9 and 1.1 were considered equivocal results.
Statistical Analysis
Statistical analyses of frequency counts were performed withthe use of the chi-square test or Fisher's exact test for smallsamples, and means were compared with the two-sample t-test.All tests were two-sided. The odds ratio was used as a measureof the risk of restenosis in patients with a given risk factoras compared with those without the risk factor. Modeling ofthe dichotomous variable of restenosis at six months was performedwith the logistic-regression model. Factors affecting the lossindex were identified by linear regression. The covariates consideredwere seropositive CMV status, higher CMV titer, diabetes, hypercholesterolemia,hypertension, location of the stenosis in the left anteriordescending coronary artery, small reference vessel (<3 mmin diameter), a recent history of smoking, male sex, older age,and unstable angina as the indication for atherectomy. All covariateswere examined as predictors of restenosis and the loss indexin univariate analyses, as a group in one multivariate model,and in a stepwise multivariable model. Values are reported asmeans ±SD.
Results
Characteristics of the Patients
The 75 patients ranged in age from 35 to 78 years (mean, 58);there were 58 men and 17 women (Table 1). Our patients weresimilar to the total OARS cohort with respect to age, sex, andthe proportion of patients with single- or double-vessel disease(Table 1), suggesting that the subgroup was representative ofthe patients undergoing directional coronary atherectomy inthe larger study.
Table 1. Characteristics of the Total Cohort in the Optimal Atherectomy Restenosis Study (OARS) and the Subgroup of Patients in the Present Study.
Forty-nine of the 75 patients (65 percent) had positive testsfor anti-CMV IgG antibodies at the time of enrollment in thestudy, indicating prior exposure to CMV — a prevalenceof seropositivity similar to that reported in several epidemiologicstudies involving subjects of a similar age.12 Of the 18 patientsexcluded from the study because an angiogram was not obtainedat six months, 11 (61 percent) were seropositive for CMV, whichis similar to the prevalence among the 75 patients includedin the study. Restenosis developed in 23 of the 75 patients(31 percent).
The prevalence of several potential risk factors for restenosisdid not differ according to the CMV status of the patients.The one exception was hypertension, which was present in 59percent of the seropositive patients but in only 31 percentof the seronegative patients (P = 0.02). Additional analysesshowed, however, that the presence of hypertension was unrelatedto restenosis (P = 0.18).
Correlation between CMV Seropositivity and Restenosis
Of the 49 patients with prior exposure to CMV, 21 (43 percent)had restenosis at six months, as compared with only 2 of the26 patients (8 percent) without prior exposure to the virus(P = 0.002) (Figure 1). When the percentage of stenosis of thetarget vessel at follow-up was analyzed as a continuous variable,CMV infection was associated with more severe stenosis (P =0.01) (Table 2 and Figure 1). The minimal luminal diameter andpercentage of stenosis at base line, immediately after directionalcoronary atherectomy, and at six months are shown in Table 2.Figure 2 shows the distribution of stenotic target vessels accordingto the minimal luminal diameter at each of the three pointsin time. At base line, the reference diameter of the vesseland the minimal luminal diameter of the stenotic segment tendedto be larger in the seropositive patients than in the seronegativepatients, but there was no significant difference in the percentageof stenosis. Immediately after the procedure, the seropositivegroup had a slightly larger minimal luminal diameter (P = 0.01),but the mean gain was similar. At six months, however, the seropositivegroup had a much greater loss of luminal diameter (P = 0.003)and, most important, an 89 percent higher loss index than theseronegative group (P<0.001) (Table 2 and Figure 3).
Figure 1. Influence of Prior Cytomegalovirus (CMV) Infection on the Distribution of Stenosis in 85 Target Vessels in 75 Patients, as Determined by Angiography Six Months after Directional Coronary Atherectomy.
The patients were divided into two groups on the basis of whether they were seropositive or seronegative for anti-CMV IgG antibodies at base line. A seropositive status was defined prospectively as an assay value of 0.25 unit or higher. At six months, vessels in the seropositive patients had a higher percentage of stenosis than vessels in the seronegative patients (P = 0.01). The inset shows the incidence of restenosis (>50 percent narrowing of the vessel diameter), which was also higher in the seropositive patients (P = 0.002).
Figure 3. Distribution of the Loss Index at Six Months.
The loss index was calculated as the late loss (the minimal luminal diameter immediately after atherectomy minus the minimal luminal diameter at six months) divided by the early gain (the minimal luminal diameter immediately after atherectomy minus the minimal luminal diameter before atherectomy), expressed as a percentage. The seropositive patients had a higher loss index than the seronegative patients (P<0.001).
Influence of CMV Seropositivity and Other Risk Factors on Restenosis
Univariate analyses (Table 3) showed that CMV seropositivitywas the only statistically significant predictor of restenosis(odds ratio, 9.0; P = 0.002). An analysis of the associationbetween the mean IgG antibody titer and restenosis confirmedthe finding (mean titer, 0.66±0.30 unit among the patientswith restenosis and 0.44±0.35 unit among those withoutrestenosis; P = 0.01). There were no other statistically significantpredictors of restenosis. The relation of CMV seropositivityand the CMV titer with the risk of restenosis did not changein the multivariate logistic-regression models (odds ratio forrestenosis associated with a positive CMV status as comparedwith a negative status, 12.9; 95 percent confidence interval,2.3 to 71.1; P = 0.003; odds ratio associated with a higherCMV titer as compared with a lower titer, 8.1; 95 percent confidenceinterval, 1.5 to 43.2; P = 0.01).
Table 3. Univariate Association between Restenosis and Potential Risk Factors.
Influence of CMV Seropositivity and Other Risk Factors on the Loss Index
Simple linear regression models showed that both the continuousvariable for the CMV status (the CMV titer) and the dichotomousvariable for the CMV status (an ELISA value >0.25 unit indicatingseropositivity and a lower value indicating seronegativity)were strong predictors of the loss index (P = 0.01 and P = 0.002,respectively).
The full multiple regression model for the loss index showedthat the CMV status, analyzed as either a continuous or a dichotomousvariable, was a persistent and independent predictor of restenosis,over and above the effects of all other covariates in the model(P = 0.03 and P = 0.01, respectively). Table 4 shows the resultsof the full model with the CMV titer. The results of multivariateanalyses of the other risk factors did not differ appreciablyfrom the results of the univariate analyses. A stepwise approachto model selection also identified the continuous and dichotomousvariables for the CMV status as the only significant predictorsof the loss index. Although the relation between the CMV titerand restenosis was significant (P = 0.01), the CMV titer accountedfor only 7 percent of the variation in the loss index at sixmonths (r2 = 0.07). To put this in perspective, taken as a whole,all the risk factors we analyzed explained only 11.5 percentof the total variation in the loss index.
Table 4. Association between Potential Risk Factors and the Loss Index.
To determine whether the effect of exposure to CMV differedin subgroups of patients defined according to the other variablesanalyzed in the study, we tested a two-factor interaction ofeach variable with CMV exposure. None of the interactions weresignificant.
Evidence against the Presence of Acute Infection and Systemic Viremia
Anti-CMV IgM antibodies, which are usually present only earlyafter the acute infection, were not detected in any of the patientsat base line. At approximately six months (when follow-up angioplastywas performed), a second assay of anti-CMV IgG antibodies showedno significant change in the titer (Figure 4). Most important,no patient who was initially seropositive for anti-CMV IgG antibodieshad a significant increase in the titer (to more than two timesthe initial value), and titers fell to the seronegative rangein only four initially seropositive patients (all of whom hadrestenosis). In addition, none of the initially seronegativepatients became seropositive.
Figure 4. Titer of Anti-CMV IgG Antibodies at Base Line and at Six Months.
A titer of 0.25 unit or higher (i.e., a value above the broken line) was considered to indicate seropositivity.
Seropositivity for Hepatitis A Virus
To determine whether the correlation between CMV seropositivityand restenosis merely reflected a generalized susceptibilityto viral infection or an increased but nonspecific immune response,we determined whether there was a correlation between preexistingantibodies to hepatitis A virus and restenosis (the frequencyof seropositivity for hepatitis A virus is approximately thesame as that for CMV). Forty-one percent of the 75 patientswere seropositive for hepatitis A virus. However, no significantassociation was found between seropositivity and restenosis.The rate of restenosis was 35.7 percent among the patients whowere seropositive for hepatitis A virus and 37.5 percent amongthose who were seronegative.
Discussion
The present study provides prospective evidence that prior exposureto CMV, as indicated by the presence of anti-CMV IgG antibodiesat the time of coronary atherectomy, is a strong independentrisk factor for restenosis. The importance of this risk factoris reflected by the odds ratio for restenosis, which was ninetimes higher among the patients who had previously been exposedto CMV than among those who had not been exposed to the virus.None of the other variables tested were associated with a significantlyincreased risk of restenosis — findings that are generallyconsistent with the results of other studies.13,14,15,16,17,18
In our primary analysis, we considered the end point of restenosisas a dichotomous variable (i.e., restenosis vs. no restenosis).However, when the degree of stenosis was considered as a continuousvariable, the patients who were seropositive for CMV had a higherpercentage of stenosis than the seronegative patients. Consideredas a continuous variable, the minimal luminal diameter immediatelyafter directional coronary atherectomy was larger in the seropositivepatients than in the seronegative patients. However, the seropositivepatients had a markedly greater loss of luminal diameter anda higher loss index at six months, resulting in a tendency towarda smaller minimal luminal diameter and a higher incidence ofrestenosis.
Given that the processes leading to restenosis are complex andundoubtedly multifactorial, it is all the more compelling thatone factor — exposure to CMV — conveyed such a highrisk. The diagnosis of restenosis in this study was based onangiographic evaluation rather than clinical assessment, whichis known to be highly inaccurate in predicting restenosis. Confidencein the results also derives from the fact that this study wasprospective in design, that the angiograms were evaluated withoutknowledge of the patients' CMV status, and that the tests foranti-CMV antibodies were performed without knowledge of theangiographic results.
The association between the development of restenosis and priorexposure to CMV was based on assays of anti-CMV IgG antibodiesperformed at the time of the atherectomy. Antibody levels didnot increase during the ensuing six months. This finding, inconjunction with the fact that anti-CMV IgM antibodies werenot detected, suggests that acute CMV infection with systemicviremia did not occur. We cannot rule out the possibility thatacute viremia developed shortly after the atherectomy, withantibody levels returning to base-line values by six months.Our results, however, are most compatible with the idea thateither the virus produced an abortive infection (i.e., the expressionof viral genes was limited to immediate early gene products)or viral replication occurred locally in the absence of systemicviremia.
CMV is a complex virus — it has a large genome with over200 open reading frames. Thus, it undoubtedly possesses manyviral proteins that may influence neointimal accumulation. Inaddition to the effects of IE84, which binds to and inactivatesp53, the infection of smooth-muscle cells with CMV leads tothe expression and secretion of growth factors,19,20 and CMVinfection has been shown to activate NF-B, a transcription factorinvolved in stimulating a broad range of genes, including thosethat have roles in inflammatory and immune responses.21 Thevirus also increases the adhesion of leukocytes and plateletsto endothelial cells by inducing cellular expression of adhesionmolecules22,23,24,25 and causes changes that are procoagulant.26,27,28Furthermore, CMV increases the activity of the scavenger receptor,and IE72, another immediate early gene product, increases theexpression of the scavenger-receptor gene.29 The increased accumulationof oxidized low-density lipoprotein cholesterol in lesionalsmooth-muscle cells may contribute to an atherogenic processsuch as restenosis. Finally, it has recently been shown thatIE72 and IE84 inhibit apoptosis, which may increase neointimalaccumulation.30
Unexpectedly, we also found a strong association between exposureto CMV and hypertension. Because this association was not aprospectively defined end point, additional studies are neededto validate the potentially important link between CMV infectionand hypertension. It is possible that the relation between CMVinfection and restenosis observed in the present investigationis due to the particular type of angioplasty used — atherectomy— and that different results would have been observedwith other types, such as balloon angioplasty. Separate studiesof other types of angioplasty will be needed to settle thisissue.
It is possible that CMV seropositivity, instead of reflectinga causal role of CMV infection in the development of restenosis,is just a marker of another process that causes restenosis.Although a causal relation has not yet been definitively demonstrated,our previous studies showed that CMV DNA is present in restenoticlesions in humans,3 a CMV gene product inhibits the transcriptionalactivity of p53 in human coronary-artery smooth-muscle cells,3and acute CMV infection increases neointimal formation in ratswith balloon injuries.31 Taken together with the results presentedhere, these findings support the idea that CMV infection playsa part in restenosis.
The results of the present investigation, if confirmed by additionallarge studies, demonstrate that CMV provides a means of stratifyingpatients according to the risk of restenosis. Thus, the knowledge(based on the results of a simple, standard blood test) thata given patient has less than a 10 percent chance of restenosis(i.e., is seronegative for CMV) or more than a 40 percent chance(i.e., is seropositive for CMV), when considered together withthe patient's specific clinical profile, may influence the clinician'sjudgment of whether that patient will benefit from atherectomyor should instead undergo coronary-artery bypass surgery. Andif future studies establish a causal role of CMV infection inthe development of restenosis, it may be possible to preventrestenosis by using specific antiviral strategies.
We are indebted to Drs. Kenneth M. Kent, Lowell F. Satler, AugustoD. Pichard, and the rest of the OARS investigators, who madethis study possible; to Dr. E.S. Huang for his invaluable adviceon the immunovirologic aspects of CMV; to Regina A. Deible,R.N., Theresa A. Bucher, R.N., and Linda Leon, B.S., for theirhelp in obtaining blood samples; to Richard Maters and his associatesfor performing the hepatitis A antibody test; and to D. Kochfor expert preparation of the manuscript.
Source Information
From the Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md. (Y.F.Z., M.A.W., Z.X.Y., T.F., S.E.E.), and the Washington Hospital Center, Washington, D.C. (M.B.L., J.J.P.).
Address reprint requests to Dr. Epstein at the Cardiology Branch, National Heart, Lung, and Blood Institute, Bldg. 10, Rm. 7B15, 10 Center Dr., MSC 1650, Bethesda, MD 20892-1650.
References
Serruys PW, Luijten HE, Beatt KJ, et al. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon: a quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation 1988;77:361-371. [Free Full Text]
Faxon DP, Currier JW. Prevention of post-PTCA restenosis. Ann N Y Acad Sci 1995;748:419-427. [Medline]
Speir E, Modali R, Huang ES, et al. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science 1994;265:391-394. [Free Full Text]
Melnick JL, Adam E, Debakey ME. Cytomegalovirus and atherosclerosis. Eur Heart J 1993;14:Suppl K:30-38.
Jordan MC, Rousseau WE, Stewart JA, Noble GR, Chin TDY. Spontaneous cytomegalovirus mononucleosis: clinical and laboratory observations in nine cases. Ann Intern Med 1973;79:153-160.
Klacsmann P. Cytomegalovirus mononucleosis. Del Med J 1977;49:399-409. [Medline]
Bruggeman CA. Cytomegalovirus and latency: an overview. Virchows Arch B Cell Pathol Incl Mol Pathol 1993;64:325-333. [Medline]
Jacobson MA, Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS): clinical findings, diagnosis, and treatment. Ann Intern Med 1988;108:585-594.
Schulman LL, Reison DS, Austin JHM, Rose EA. Cytomegalovirus pneumonitis after cardiac transplantation. Arch Intern Med 1991;151:1118-1124. [Free Full Text]
Southern P, Oldstone MBA. Medical consequences of persistent viral infection. N Engl J Med 1986;314:359-367. [Medline]
Geist LJ, Monick MM, Stinski MF, Hunninghake GW. The immediate early genes of human cytomegalovirus upregulate expression of the interleukin-2 and interleukin-2 receptor genes. Am J Respir Cell Mol Biol 1991;5:292-296.
Bach R, Jung F, Kohsiek I, et al. Factors affecting the restenosis rate after percutaneous transluminal coronary angioplasty. Thromb Res 1994;74:Suppl 1:S55-S67.
Hermans WRM, Rensing BJ, Foley DP, et al. Patient, lesion, and procedural variables as risk factors for luminal re-narrowing after successful coronary angioplasty: a quantitative analysis in 653 patients with 778 lesions. J Cardiovasc Pharmacol 1993;22:Suppl 4:S45-S57.
Le Feuvre CL, Bonan R, Lesperance J, Gosselin G, Joyal M, Crepeau J. Predictive factors of restenosis after multivessel percutaneous transluminal coronary angioplasty. Am J Cardiol 1994;73:840-844. [CrossRef][Medline]
Dzavik V, Teo KK, Yokoyama S, et al. Effect of serum lipid concentrations on restenosis after successful de novo percutaneous transluminal coronary angioplasty in patients with total cholesterol 160 to 240 mg/dl and triglycerides <350 mg/dl. Am J Cardiol 1995;75:936-938. [CrossRef][Medline]
Stein B, Weintraub WS, Gebhart SP, et al. Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty. Circulation 1995;91:979-989. [Free Full Text]
Foley DP, Melkert R, Serruys PW. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation 1994;90:1239-1251. [Free Full Text]
Gonczol E, Plotkin SA. Cells infected with human cytomegalovirus release a factor(s) that stimulates cell DNA synthesis. J Gen Virol 1984;65:1833-1837. [Free Full Text]
Alcami J, Barzu T, Michelson S. Induction of an endothelial cell growth factor by human cytomegalovirus infection of fibroblasts. J Gen Virol 1991;72:2765-2770. [Free Full Text]
Kowalik TF, Wing B, Haskill JS, Azizkhan JC, Baldwin AS Jr, Huang ES. Multiple mechanisms are implicated in the regulation of NF-kappa B activity during human cytomegalovirus infection. Immunology 1993;78:405-412. [Medline]
Grundy JE, Downes KL. Up-regulation of LFA-3 and ICAM-1 on the surface of fibroblasts infected with cytomegalovirus. Immunology 1993;78:405-412.
O'Brien KD, Allen MD, McDonald TO, et al. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques: implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 1993;92:945-951.
Span AH, van Dam-Mieras MC, Mullers W, Endert J, Muller AD, Bruggeman CA. The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells. Eur J Clin Invest 1991;21:331-338. [Medline]
Etingin OR, Silverstein RL, Hajjar DP. von Willebrand factor mediates platelet adhesion to virally infected endothelial cells. Proc Natl Acad Sci U S A 1993;90:5153-5156. [Free Full Text]
van Dam-Mieras MCE, Muller AD, van Hinsbergh VWM, Mullers WJ, Bomans PH, Bruggeman CA. The procoagulant response of cytomegalovirus infected endothelial cells. Thromb Haemost 1992;68:364-370. [Medline]
Etingin OR, Silverstein RL, Friedman HM, Hajjar DP. Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells. Cell 1990;61:657-662. [CrossRef][Medline]
Pryzdial ELG, Wright JF. Prothrombinase assembly on an enveloped virus: evidence that the cytomegalovirus surface contains procoagulant phospholipid. Blood 1994;84:3749-3757. [Free Full Text]
Zhou YF, Guetta E, Yu ZX, Finkel T, Epstein SE. Human cytomegalovirus, through its immediate early gene product IE72, directly activates transcription of the scavenger receptor gene in human aortic smooth muscle cells. Circulation 1995;92:Suppl I:I-162.abstract
Zhu H, Shen Y, Shenk T. Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J Virol 1995;69:7960-7970. [Abstract]
Zhou YF, Shou M, Guzman R, Guetta E, Finkel T, Epstein SE. Cytomegalovirus infection increases neointimal formation in the rat model of balloon injury. J Am Coll Cardiol 1995;25:242a-242a.abstract
Simanek, A. M, Dowd, J. B., Aiello, A. E
(2009). Persistent pathogens linking socioeconomic position and cardiovascular disease in the US. Int J Epidemiol
38: 775-787
[Abstract][Full Text]
Qian, Z., Xuan, B., Hong, T. T., Yu, D.
(2008). The Full-Length Protein Encoded by Human Cytomegalovirus Gene UL117 Is Required for the Proper Maturation of Viral Replication Compartments. J. Virol.
82: 3452-3465
[Abstract][Full Text]
Michaelis, M., Ha, T. A. T., Doerr, H. W., Cinatl, J. Jr
(2008). Valproic acid interferes with antiviral treatment in human cytomegalovirus-infected endothelial cells. Cardiovasc Res
77: 544-550
[Abstract][Full Text]
Bolovan-Fritts, C. A., Spector, S. A.
(2008). Endothelial damage from cytomegalovirus-specific host immune response can be prevented by targeted disruption of fractalkine-CX3CR1 interaction. Blood
111: 175-182
[Abstract][Full Text]
Krebs, P., Scandella, E., Bolinger, B., Engeler, D., Miller, S., Ludewig, B.
(2007). Chronic Immune Reactivity Against Persisting Microbial Antigen in the Vasculature Exacerbates Atherosclerotic Lesion Formation. Arterioscler. Thromb. Vasc. Bio.
27: 2206-2213
[Abstract][Full Text]
Bolovan-Fritts, C. A., Trout, R. N., Spector, S. A.
(2007). High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage. Blood
110: 1857-1863
[Abstract][Full Text]
Sanz-Gonzalez, S. M., Barquin, L., Garcia-Cao, I., Roque, M., Gonzalez, J. M., Fuster, J. J., Castells, M. T., Flores, J. M., Serrano, M., Andres, V.
(2007). Increased p53 gene dosage reduces neointimal thickening induced by mechanical injury but has no effect on native atherosclerosis. Cardiovasc Res
75: 803-812
[Abstract][Full Text]
Shen, P., Niu, G., Yao, M., Wang, H., Fei, J.
(2007). Studying on the 19-bp Palindrome Repeats in Human Cytomegalovirus Immediate Early Enhancer/Promoter Reveals their Diversity in Function for the Promoter Activity. J Biochem
142: 25-31
[Abstract][Full Text]
Terhune, S., Torigoi, E., Moorman, N., Silva, M., Qian, Z., Shenk, T., Yu, D.
(2007). Human Cytomegalovirus UL38 Protein Blocks Apoptosis. J. Virol.
81: 3109-3123
[Abstract][Full Text]
Bentz, G. L., Jarquin-Pardo, M., Chan, G., Smith, M. S., Sinzger, C., Yurochko, A. D.
(2006). Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naive Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV. J. Virol.
80: 11539-11555
[Abstract][Full Text]
Yang, X., Murthy, V., Schultz, K., Tatro, J. B., Fitzgerald, K. A., Beasley, D.
(2006). Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol.
291: H2334-H2343
[Abstract][Full Text]
Reinhardt, B., Winkler, M., Schaarschmidt, P., Pretsch, R., Zhou, S., Vaida, B., Schmid-Kotsas, A., Michel, D., Walther, P., Bachem, M., Mertens, T.
(2006). Human cytomegalovirus-induced reduction of extracellular matrix proteins in vascular smooth muscle cell cultures: a pathomechanism in vasculopathies?. J. Gen. Virol.
87: 2849-2858
[Abstract][Full Text]
Sanchez, V., Spector, D. H.
(2006). Cyclin-Dependent Kinase Activity Is Required for Efficient Expression and Posttranslational Modification of Human Cytomegalovirus Proteins and for Production of Extracellular Particles.. J. Virol.
80: 5886-5896
[Abstract][Full Text]
Froberg, M. K., Dannen, D., Adams, A., Parker-Thornburg, J., Kolattukudy, P.
(2006). Murine Cytomegalovirus Infection Markedly Reduces Serum MCP-1 Levels in MCP-1 Transgenic Mice.. Annals of Clinical & Laboratory Science
36: 179-184
[Abstract][Full Text]
Shen, Y. H., Zhang, L., Utama, B., Wang, J., Gan, Y., Wang, X., Wang, J., Chen, L., Vercellotti, G. M., Coselli, J. S., Mehta, J. L., Wang, X. L.
(2006). Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10). Cardiovasc Res
69: 502-511
[Abstract][Full Text]
Ryckman, B. J., Jarvis, M. A, Drummond, D. D., Nelson, J. A., Johnson, D. C.
(2006). Human Cytomegalovirus Entry into Epithelial and Endothelial Cells Depends on Genes UL128 to UL150 and Occurs by Endocytosis and Low-pH Fusion. J. Virol.
80: 710-722
[Abstract][Full Text]
Walsh, D., Perez, C., Notary, J., Mohr, I.
(2005). Regulation of the Translation Initiation Factor eIF4F by Multiple Mechanisms in Human Cytomegalovirus-Infected Cells. J. Virol.
79: 8057-8064
[Abstract][Full Text]
Oshima, T., Ozono, R., Yano, Y., Oishi, Y., Teragawa, H., Higashi, Y., Yoshizumi, M., Kambe, M.
(2005). Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects. J Am Coll Cardiol
45: 1219-1222
[Abstract][Full Text]
Rahbar, A., Soderberg-Naucler, C.
(2005). Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation. J. Virol.
79: 2211-2220
[Abstract][Full Text]
Casarosa, P., Waldhoer, M., LiWang, P. J., Vischer, H. F., Kledal, T., Timmerman, H., Schwartz, T. W., Smit, M. J., Leurs, R.
(2005). CC and CX3C Chemokines Differentially Interact with the N Terminus of the Human Cytomegalovirus-encoded US28 Receptor. J. Biol. Chem.
280: 3275-3285
[Abstract][Full Text]
Reinhardt, B., Schaarschmidt, P., Bossert, A., Luske, A., Finkenzeller, G., Mertens, T., Michel, D.
(2005). Upregulation of functionally active vascular endothelial growth factor by human cytomegalovirus. J. Gen. Virol.
86: 23-30
[Abstract][Full Text]
Bolovan-Fritts, C. A., Trout, R. N., Spector, S. A.
(2004). Human Cytomegalovirus-Specific CD4+-T-Cell Cytokine Response Induces Fractalkine in Endothelial Cells. J. Virol.
78: 13173-13181
[Abstract][Full Text]
Reeves, M. B., Coleman, H., Chadderton, J., Goddard, M., Sissons, J. G. P., Sinclair, J. H.
(2004). Vascular endothelial and smooth muscle cells are unlikely to be major sites of latency of human cytomegalovirus in vivo. J. Gen. Virol.
85: 3337-3341
[Abstract][Full Text]
Evers, D. L., Komazin, G., Ptak, R. G., Shin, D., Emmer, B. T., Townsend, L. B., Drach, J. C.
(2004). Inhibition of Human Cytomegalovirus Replication by Benzimidazole Nucleosides Involves Three Distinct Mechanisms. Antimicrob. Agents Chemother.
48: 3918-3927
[Abstract][Full Text]
Toutouzas, K., Colombo, A., Stefanadis, C.
(2004). Inflammation and restenosis after percutaneous coronary interventions. Eur Heart J
25: 1679-1687
[Abstract][Full Text]
Ludewig, B., Krebs, P., Scandella, E.
(2004). Immunopathogenesis of atherosclerosis. J. Leukoc. Biol.
76: 300-306
[Abstract][Full Text]
Leis, M., Marschall, M., Stamminger, T.
(2004). Downregulation of the cellular adhesion molecule Thy-1 (CD90) by cytomegalovirus infection of human fibroblasts. J. Gen. Virol.
85: 1995-2000
[Abstract][Full Text]
Shen, Y.H., Utama, B., Wang, J., Raveendran, M., Senthil, D., Waldman, W.J., Belcher, J.D., Vercellotti, G., Martin, D., Mitchelle, B.M., Wang, X.L.
(2004). Human Cytomegalovirus Causes Endothelial Injury Through the Ataxia Telangiectasia Mutant and p53 DNA Damage Signaling Pathways. Circ. Res.
94: 1310-1317
[Abstract][Full Text]
Froberg, M. K.
(2004). CMV Escapes!. Annals of Clinical & Laboratory Science
34: 123-130
[Abstract][Full Text]
Nerheim, P. L., Meier, J. L., Vasef, M. A., Li, W.-G., Hu, L., Rice, J. B., Gavrila, D., Richenbacher, W. E., Weintraub, N. L.
(2004). Enhanced Cytomegalovirus Infection in Atherosclerotic Human Blood Vessels. Am. J. Pathol.
164: 589-600
[Abstract][Full Text]
Mnjoyan, Z. H., Dutta, R., Zhang, D., Teng, B.-B., Fujise, K.
(2003). Paradoxical Upregulation of Tumor Suppressor Protein p53 in Serum-Stimulated Vascular Smooth Muscle Cells: A Novel Negative-Feedback Regulatory Mechanism. Circulation
108: 464-471
[Abstract][Full Text]
Lin, T-M, Chen, W-j, Chen, H-Y, Wang, P-W, Eng, H-L
(2003). Increased incidence of cytomegalovirus but not Chlamydia pneumoniae in atherosclerotic lesions of arteries of lower extremities from patients with diabetes mellitus undergoing amputation. J. Clin. Pathol.
56: 429-432
[Abstract][Full Text]
Smieja, M., Gnarpe, J., Lonn, E., Gnarpe, H., Olsson, G., Yi, Q., Dzavik, V., McQueen, M., Yusuf, S., for the Heart Outcomes Prevention Evaluation (HOPE,
(2003). Multiple Infections and Subsequent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation
107: 251-257
[Abstract][Full Text]
Horne, B. D., Muhlestein, J. B., Carlquist, J. F., Bair, T. L., Madsen, T. E., Hart, N. I., Anderson, J. L., for the Intermountain Heart Collaborative (IHC) St,
(2003). Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Coronary Disease. Circulation
107: 258-263
[Abstract][Full Text]
Kronschnabl, M., Stamminger, T.
(2003). Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site. J. Gen. Virol.
84: 61-73
[Abstract][Full Text]
Maisch, T., Kropff, B., Sinzger, C., Mach, M.
(2002). Upregulation of CD40 Expression on Endothelial Cells Infected with Human Cytomegalovirus. J. Virol.
76: 12803-12812
[Abstract][Full Text]
Suzuki, K., Murtuza, B., Suzuki, N., Khan, M., Kaneda, Y., Yacoub, M. H.
(2002). Human Cytomegalovirus Immediate-Early Protein IE2-86, but not IE1-72, Causes Graft Coronary Arteriopathy in the Transplanted Rat Heart. Circulation
106: I-158-I-162
[Abstract][Full Text]
Prasad, A., Zhu, J., Halcox, J. P.J., Waclawiw, M. A., Epstein, S. E., Quyyumi, A. A.
(2002). Predisposition to Atherosclerosis by Infections: Role of Endothelial Dysfunction. Circulation
106: 184-190
[Abstract][Full Text]
Fortunato, E. A., Sanchez, V., Yen, J. Y., Spector, D. H.
(2002). Infection of Cells with Human Cytomegalovirus during S Phase Results in a Blockade to Immediate-Early Gene Expression That Can Be Overcome by Inhibition of the Proteasome. J. Virol.
76: 5369-5379
[Abstract][Full Text]
Mulvihill, N T, Foley, J B
(2002). Inflammation in acute coronary syndromes. Heart
87: 201-204
[Abstract][Full Text]
Sanchez, V., Clark, C. L., Yen, J. Y., Dwarakanath, R., Spector, D. H.
(2002). Viable Human Cytomegalovirus Recombinant Virus with an Internal Deletion of the IE2 86 Gene Affects Late Stages of Viral Replication. J. Virol.
76: 2973-2989
[Abstract][Full Text]
Hansson, G. K.
(2001). Immune Mechanisms in Atherosclerosis. Arterioscler. Thromb. Vasc. Bio.
21: 1876-1890
[Abstract][Full Text]
Agema, W. R. P., Jukema, J. W., Pimstone, S. N., Kastelein, J. J. P.
(2001). Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy. Eur Heart J
22: 2058-2074
George, J., Greenberg, S., Barshack, I., Singh, M., Pri-Chen, S., Laniado, S., Keren, G.
(2001). Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70. J Am Coll Cardiol
38: 1564-1569
[Abstract][Full Text]
Buerger, I., Reefschlaeger, J., Bender, W., Eckenberg, P., Popp, A., Weber, O., Graeper, S., Klenk, H.-D., Ruebsamen-Waigmann, H., Hallenberger, S.
(2001). A Novel Nonnucleoside Inhibitor Specifically Targets Cytomegalovirus DNA Maturation via the UL89 and UL56 Gene Products. J. Virol.
75: 9077-9086
[Abstract][Full Text]
Neumann, F.-J., Kastrati, A., Miethke, T., Mehilli, J., Pogatsa-Murray, G., Koch, W., Seyfarth, M., Schomig, A.
(2001). Previous Cytomegalovirus Infection and Restenosis After Coronary Stent Placement. Circulation
104: 1135-1139
[Abstract][Full Text]
DIEZ-JUAN, A., ANDRES, V.
(2001). The growth suppressor p27Kip1 protects against diet-induced atherosclerosis. FASEB J.
15: 1989-1995
[Abstract][Full Text]
Blankenberg, S., Rupprecht, H. J., Bickel, C., Espinola-Klein, C., Rippin, G., Hafner, G., Ossendorf, M., Steinhagen, K., Meyer, J.
(2001). Cytomegalovirus Infection With Interleukin-6 Response Predicts Cardiac Mortality in Patients With Coronary Artery Disease. Circulation
103: 2915-2921
[Abstract][Full Text]
Zhu, J., Shearer, G. M., Marincola, F. M., Norman, J. E., Rott, D., Zou, J.-P., Epstein, S. E.
(2001). Discordant cellular and humoral immune responses to cytomegalovirus infection in healthy blood donors: existence of a Th1-type dominant response. Int Immunol
13: 785-790
[Abstract][Full Text]
Patel, N. H., Jindal, R. M., Wilkin, T., Rose, S., Johnson, M. S., Shah, H., Namyslowski, J., Moresco, K. P., Trerotola, S. O.
(2001). Renal Arterial Stenosis in Renal Allografts: Retrospective Study of Predisposing Factors and Outcome after Percutaneous Transluminal Angioplasty. Radiology
219: 663-667
[Abstract][Full Text]
Froberg, M. K., Seacotte, N., Dahlberg, E.
(2001). Cytomegalovirus Seropositivity and Serum Total Cholesterol Levels in Young Patients. Annals of Clinical & Laboratory Science
31: 157-161
[Abstract][Full Text]
BRENNAN, D. C.
(2001). Cytomegalovirus in Renal Transplantation. J. Am. Soc. Nephrol.
12: 848-855
[Full Text]
Burian, K., Kis, Z., Virok, D., Endresz, V., Prohaszka, Z., Duba, J., Berencsi, K., Boda, K., Horvath, L., Romics, L., Fust, G., Gonczol, E.
(2001). Independent and Joint Effects of Antibodies to Human Heat-Shock Protein 60 and Chlamydia pneumoniae Infection in the Development of Coronary Atherosclerosis. Circulation
103: 1503-1508
[Abstract][Full Text]
Schiele, F, Batur, M K, Seronde, M F, Meneveau, N, Sewoke, P, Bassignot, A, Couetdic, G, Caulfield, F, Bassand, J-P
(2001). Cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori IgG antibodies and restenosis after stent implantation: an angiographic and intravascular ultrasound study. Heart
85: 304-311
[Abstract][Full Text]
Zhu, J., Nieto, F. J., Horne, B. D., Anderson, J. L., Muhlestein, J. B., Epstein, S. E.
(2001). Prospective Study of Pathogen Burden and Risk of Myocardial Infarction or Death. Circulation
103: 45-51
[Abstract][Full Text]
Naghavi, M., Barlas, Z., Siadaty, S., Naguib, S., Madjid, M., Casscells, W.
(2000). Association of Influenza Vaccination and Reduced Risk of Recurrent Myocardial Infarction. Circulation
102: 3039-3045
[Abstract][Full Text]
Muhlestein, J. B., Horne, B. D., Carlquist, J. F., Madsen, T. E., Bair, T. L., Pearson, R. R., Anderson, J. L.
(2000). Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease. Circulation
102: 1917-1923
[Abstract][Full Text]
Castillo, J. P., Yurochko, A. D., Kowalik, T. F.
(2000). Role of Human Cytomegalovirus Immediate-Early Proteins in Cell Growth Control. J. Virol.
74: 8028-8037
[Abstract][Full Text]
Espinola-Klein, C., Rupprecht, H.-J., Blankenberg, S., Bickel, C., Kopp, H., Rippin, G., Hafner, G., Pfeifer, U., Meyer, J.
(2000). Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes Simplex Virus Infection?. Stroke
31: 2127-2133
[Abstract][Full Text]
Alber, D. G., Powell, K. L., Vallance, P., Goodwin, D. A., Grahame-Clarke, C.
(2000). Herpesvirus Infection Accelerates Atherosclerosis in the Apolipoprotein E-Deficient Mouse. Circulation
102: 779-785
[Abstract][Full Text]
Fong, I. W.
(2000). Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. CMAJ
163: 49-56
[Abstract][Full Text]
Camm, A.J., Fox, K.M.
(2000). Chlamydia pneumonia (and other infective agents) in atherosclerosis and acute coronary syndromes. How good is the evidence?. Eur Heart J
21: 1046-1051
GRIMES, D.S., HINDLE, E., DYER, T.
(2000). Respiratory infection and coronary heart disease: progression of a paradigm. QJM
93: 375-383
[Abstract][Full Text]
Epstein, S. E., Zhu, J., Burnett, M. S., Zhou, Y. F., Vercellotti, G., Hajjar, D.
(2000). Infection and Atherosclerosis : Potential Roles of Pathogen Burden and Molecular Mimicry. Arterioscler. Thromb. Vasc. Bio.
20: 1417-1420
[Abstract][Full Text]
Moreno, P. R., Palacios, I. F.
(2000). Cytomegalovirus and Restenosis After Percutaneous Transluminal Coronary Angioplasty. Circulation
101
: e163-e163
[Full Text]
Matsushita, H., Morishita, R., Aoki, M., Tomita, N., Taniyama, Y., Nakagami, H., Shimozato, T., Higaki, J., Kaneda, Y., Ogihara, T.
(2000). Transfection of Antisense p53 Tumor Suppressor Gene Oligodeoxynucleotides Into Rat Carotid Artery Results in Abnormal Growth of Vascular Smooth Muscle Cells. Circulation
101: 1447-1452
[Abstract][Full Text]
Zhou, Y. F., Shou, M., Harrell, R. F, Yu, Z. X., Unger, E. F, Epstein, S. E
(2000). Chronic non-vascular cytomegalovirus infection: effects on the neointimal response to experimental vascular injury. Cardiovasc Res
45: 1019-1025
[Abstract][Full Text]
Kotenko, S. V., Saccani, S., Izotova, L. S., Mirochnitchenko, O. V., Pestka, S.
(2000). Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc. Natl. Acad. Sci. USA
97: 1695-1700
[Abstract][Full Text]
Roivainen, M., Viik-Kajander, M., Palosuo, T., Toivanen, P., Leinonen, M., Saikku, P., Tenkanen, L., Manninen, V., Hovi, T., Manttari, M.
(2000). Infections, Inflammation, and the Risk of Coronary Heart Disease. Circulation
101: 252-257
[Abstract][Full Text]
Neumann, F.-J., Kastrati, A., Miethke, T., Pogatsa-Murray, G., Seyfarth, M., Schomig, A.
(2000). Previous Cytomegalovirus Infection and Risk of Coronary Thrombotic Events After Stent Placement. Circulation
101: 11-13
[Abstract][Full Text]
Baldwin, B. R., Zhang, C.-O., Keay, S.
(2000). Cloning and epitope mapping of a functional partial fusion receptor for human cytomegalovirus gH. J. Gen. Virol.
81: 27-35
[Abstract][Full Text]
Wiedermann, C. J., Kiechl, S., Dunzendorfer, S., Schratzberger, P., Egger, G., Oberhollenzer, F., Willeit, J.
(1999). Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: Prospective results from the bruneck study. J Am Coll Cardiol
34: 1975-1981
[Abstract][Full Text]
Zhu, J., Quyyumi, A. A., Norman, J. E., Csako, G., Epstein, S. E.
(1999). Cytomegalovirus in the pathogenesis of atherosclerosis: The role of inflammation as reflected by elevated C-reactive protein levels. J Am Coll Cardiol
34: 1738-1743
[Abstract][Full Text]
Chung, M., Kizhatil, K., Albritton, L. M., Gaulton, G. N.
(1999). Induction of Syncytia by Neuropathogenic Murine Leukemia Viruses Depends on Receptor Density, Host Cell Determinants, and the Intrinsic Fusion Potential of Envelope Protein. J. Virol.
73: 9377-9385
[Abstract][Full Text]
Rossignol, D. A., Kipreos, B., Akosah, K., Mohanty, P. K.
(1999). Accelerated Transplant Coronary Artery Disease and Massive Silent Acute Myocardial Infarction in a Heart Transplant Patient: A Case Report and Brief Review of Literature. ANGIOLOGY
50: 947-953
[Abstract]
Zhou, Y. F., Shou, M., Guetta, E., Guzman, R., Unger, E. F., Yu, Z. X., Zhang, J., Finkel, T., Epstein, S. E.
(1999). Cytomegalovirus Infection of Rats Increases the Neointimal Response to Vascular Injury Without Consistent Evidence of Direct Infection of the Vascular Wall. Circulation
100: 1569-1575
[Abstract][Full Text]
Aoki, M., Morishita, R., Matsushita, H., Hayashi, S.-i., Nakagami, H., Yamamoto, K., Moriguchi, A., Kaneda, Y., Higaki, J., Ogihara, T.
(1999). Inhibition of the p53 Tumor Suppressor Gene Results in Growth of Human Aortic Vascular Smooth Muscle Cells : Potential Role of p53 in Regulation of Vascular Smooth Muscle Cell Growth. Hypertension
34: 192-200
[Abstract][Full Text]
Epstein, S. E., Zhou, Y. F., Zhu, J.
(1999). Infection and Atherosclerosis : Emerging Mechanistic Paradigms. Circulation
100
: e20-e28
[Abstract][Full Text]
Valantine, H. A., Gao, S.-Z., Menon, S. G., Renlund, D. G., Hunt, S. A., Oyer, P., Stinson, E. B., Brown, B. W. Jr, Merigan, T. C., Schroeder, J. S.
(1999). Impact of Prophylactic Immediate Posttransplant Ganciclovir on Development of Transplant Atherosclerosis : A Post Hoc Analysis of a Randomized, Placebo-Controlled Study. Circulation
100: 61-66
[Abstract][Full Text]
Tanaka, K., Zou, J.-P., Takeda, K., Ferrans, V. J., Sandford, G. R., Johnson, T. M., Finkel, T., Epstein, S. E.
(1999). Effects of Human Cytomegalovirus Immediate-Early Proteins on p53-mediated Apoptosis in Coronary Artery Smooth Muscle Cells. Circulation
99: 1656-1659
[Abstract][Full Text]
Bertrand, M. E., Bauters, C.
(1999). Cytomegalovirus Infection and Coronary Restenosis. Circulation
99: 1278-1279
[Full Text]
Manegold, C., Alwazzeh, M., Jablonowski, H., Adams, O., Medve, M., Seidlitz, B., Heidland, U., Haussinger, D., Strauer, B.-E., Heintzen, M. P.
(1999). Prior Cytomegalovirus Infection and the Risk of Restenosis After Percutaneous Transluminal Coronary Balloon Angioplasty. Circulation
99: 1290-1294
[Abstract][Full Text]
Bartels, C., Maass, M., Bein, G., Malisius, R., Brill, N., Bechtel, J. F. M., Sayk, F., Feller, A. C., Sievers, H.-H.
(1999). Detection of Chlamydia pneumoniae But Not Cytomegalovirus in Occluded Saphenous Vein Coronary Artery Bypass Grafts. Circulation
99: 879-882
[Abstract][Full Text]
Pahor, M., Elam, M. B., Garrison, R. J., Kritchevsky, S. B., Applegate, W. B.
(1999). Emerging Noninvasive Biochemical Measures to Predict Cardiovascular Risk. Arch Intern Med
159: 237-245
[Abstract][Full Text]
HALLORAN, P. F., MELK, A., BARTH, C.
(1999). Rethinking Chronic Allograft Nephropathy: The Concept of AcceleratedSenescence. J. Am. Soc. Nephrol.
10: 167-181
[Full Text]
Ridker, P. M., Hennekens, C. H., Stampfer, M. J., Wang, F.
(1998). Prospective Study of Herpes Simplex Virus, Cytomegalovirus, and the Risk of Future Myocardial Infarction and Stroke. Circulation
98: 2796-2799
[Abstract][Full Text]
Caligiuri, G., Liuzzo, G., Biasucci, L. M., Maseri, A.
(1998). Immune system activation follows inflammation in unstable angina: pathogenetic implications. J Am Coll Cardiol
32: 1295-1304
[Abstract][Full Text]
Presti, R. M., Pollock, J. L., Dal Canto, A. J., O'Guin, A. K., Virgin, H. W. IV
(1998). Interferon {gamma} Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels. JEM
188: 577-588
[Abstract][Full Text]
Speir, E., Yu, Z.-X., Ferrans, V. J., Huang, E.-S., Epstein, S. E.
(1998). Aspirin Attenuates Cytomegalovirus Infectivity and Gene Expression Mediated by Cyclooxygenase-2 in Coronary Artery Smooth Muscle Cells. Circ. Res.
83: 210-216
[Abstract][Full Text]
Anderson, J. L., Carlquist, J. F., Muhlestein, J. B., Horne, B. D., Elmer, S. P.
(1998). Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. J Am Coll Cardiol
32: 35-41
[Abstract][Full Text]
Kastrati, A., Schomig, A., Elezi, S., Schuhlen, H., Wilhelm, M., Dirschinger, J.
(1998). Interlesion Dependence of the Risk for Restenosis in Patients With Coronary Stent Placement in Multiple Lesions. Circulation
97: 2396-2401
[Abstract][Full Text]
Krosky, P. M., Underwood, M. R., Turk, S. R., Feng, K. W.-H., Jain, R. K., Ptak, R. G., Westerman, A. C., Biron, K. K., Townsend, L. B., Drach, J. C.
(1998). Resistance of Human Cytomegalovirus to Benzimidazole Ribonucleosides Maps to Two Open Reading Frames: UL89 and UL56. J. Virol.
72: 4721-4728
[Abstract][Full Text]
Ridker, P. M.
(1998). Inflammation, Infection, and Cardiovascular Risk : How Good Is the Clinical Evidence?. Circulation
97: 1671-1674
[Full Text]
Nicholson, A. C., Hajjar, D. P.
(1998). Herpesviruses in Atherosclerosis and Thrombosis : Etiologic Agents or Ubiquitous Bystanders?. Arterioscler. Thromb. Vasc. Bio.
18: 339-348
[Abstract][Full Text]
Kritchevsky, D.
(1998). History of Recommendations to the Public about Dietary Fat. J. Nutr.
128: 449-449
[Abstract][Full Text]
Sutherland, M. R., Raynor, C. M., Leenknegt, H., Wright, J. F., Pryzdial, E. L. G.
(1997). Coagulation initiated on herpesviruses. Proc. Natl. Acad. Sci. USA
94: 13510-13514
[Abstract][Full Text]
Libby, P., Egan, D., Skarlatos, S.
(1997). Roles of Infectious Agents in Atherosclerosis and Restenosis: An Assessment of the Evidence and Need for Future Research. Circulation
96: 4095-4103
[Full Text]
Persoons, M. C.J, Daemen, M. J.A.P, van Kleef, E. M, Grauls, G. E.L.M, Wijers, E., Bruggeman, C. A
(1997). Neointimal smooth muscle cell phenotype is important in its susceptibility to cytomegalovirus (CMV) infection: a study in rat. Cardiovasc Res
36: 282-288
[Abstract][Full Text]
B, a transcription factor involved in stimulating a broad range of genes, including those that have roles in inflammatory and immune responses.21 The virus also increases the adhesion of leukocytes and platelets to endothelial cells by inducing cellular expression of adhesion molecules22,23,24,25 and causes changes that are procoagulant.26,27,28 Furthermore, CMV increases the activity of the scavenger receptor, and IE72, another immediate early gene product, increases the expression of the scavenger-receptor gene.29 The increased accumulation of oxidized low-density lipoprotein cholesterol in lesional smooth-muscle cells may contribute to an atherogenic process such as restenosis. Finally, it has recently been shown that IE72 and IE84 inhibit apoptosis, which may increase neointimal accumulation.30 
Previous
