Evidence for the role of Epstein Barr Virus infections in the pathogenesis of acute coronary events.
BACKGROUND
The role of viral infections in the pathogenesis of atherosclerosis remains controversial largely due to inconsistent detection of the virus in atherosclerotic lesions. However, viral infections elicit a pro-inflammatory cascade known to be atherogenic and to precipitate acute ischemic events. We have published in vitro data that provide the foundation for a mechanism that reconciles these conflicting observations. To determine the relation between an early viral protein, deoxyuridine triphosphate nucleotidohydrolase (dUTPase), produced following reactivation of Epstein Barr Virus (EBV) to circulating pro-inflammatory cytokines, intercellular adhesion molecule-1 (ICAM-1) and acute coronary events.


RESULTS
Blood samples were obtained from 299 patients undergoing percutaneous coronary intervention for stable angina (SA), unstable angina (UA), or acute myocardial infarction (AMI). Plasma concentrations of pro-inflammatory cytokines and neutralizing antibody against EBV-encoded dUTPase were compared in the three patient groups. AMI was associated with the highest measures of interleukin-6 (ANOVA p<0.05; 4.6 ± 2.6 pg/mL in patients with AMI vs. 3.2 ± 2.3 pg/mL in SA). ICAM-1 was significantly higher in patients with AMI (ANOVA p<0.05; 304 ± 116 pg/mL in AMI vs. 265 ± 86 pg/mL SA). The highest values of ICAM-1 were found in patients having an AMI and who were antibody positive for dUTPase (ANOVA p=0.008; 369 ± 183 pg/mL in AMI and positive for dUTPase vs. 249 ± 70 pg/mL in SA negative for dUTPase antibody).


CONCLUSIONS
These clinical data support a model, based on in vitro studies, by which EBV may precipitate AMI even under conditions of low viral load through the pro-inflammatory action of the early protein dUTPase that is produced even during incomplete viral replication. They further support the putative role of viral infections in the pathogenesis of atherosclerosis and coronary artery events.
Division of Cardiovascular Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA. Philip.Binkley@osumc.edu
Philip F
PF
Binkley
Glen E
GE
Cooke
Amanda
A
Lesinski
Mackenzie
M
Taylor
Min
M
Chen
Bryon
B
Laskowski
W James
WJ
Waldman
Maria E
ME
Ariza
Marshall V
MV
Williams
Deborah A
DA
Knight
Ronald
R
Glaser
D000368:Aged; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000097:blood / Q000601:surgery / Q000821:virology; D000789:Angina, Unstable / Q000097:blood / Q000601:surgery / Q000821:virology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000601:surgery / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000601:surgery / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000601:surgery / Q000821:virology; D062645:Percutaneous Coronary Intervention; D011755:Pyrophosphatases / Q000097:blood* / Q000276:immunology; D014764:Viral Proteins / Q000097:blood / Q000276:immunology
D057134:Antibodies, Neutralizing; D018836:Inflammation Mediators; D015850:Interleukin-6; D014764:Viral Proteins; D018799:Intercellular Adhesion Molecule-1; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase