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(Circulation. 2009;119:3133-3141.)
© 2009 American Heart Association, Inc.

Contemporary Reviews in Cardiovascular Medicine

Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture

Stephen E. Epstein, MD; Jianhui Zhu, MD; Amir H. Najafi, MD; Mary S. Burnett, PhD

From the Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC.

Correspondence to Stephen E. Epstein, MD, Cardiovascular Research Institute, Washington Hospital Center, 110 Irving St NW, Suite 4B-1, Washington, DC 20010. E-mail stephen.epstein@medstar.net

Key Words: atherosclerosis • infection • inflammation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The potential contribution of infection to the induction and progression of atherosclerosis has been characterized by profound controversy, continuing to the present time. Controversy also surrounds the concept that infection can precipitate plaque rupture, an event complicating the course of atherosclerosis and clinically characterized by acute myocardial infarction and death. The purpose of this article is (1) to review what we believe are the most compelling data that either are compatible with or refute the concept that infection plays a role in atherogenesis or plaque rupture; (2) to present the mechanisms that may contribute to such effects; and (3) to discuss the impact on the infection/atherosclerosis paradigm of the recent negative therapeutic trials examining the effects of macrolide antibiotics on cardiovascular end points in patients with coronary artery disease (CAD).

	Evidence Suggesting That Pathogens Contribute to Atherogenesis

 
Although anecdotal information existed for many years suggesting that acute infection can trigger an acute myocardial infarction,^1,2 it was the groundbreaking work by Minick and Fabricant and their coworkers^3,4 in the1970s that began the serious scientific exploration of the relation between infection and atherosclerosis. These investigators demonstrated that Marek’s disease virus, an avian herpesvirus, caused atherosclerotic-like lesions in multiple arteries of chickens and that infection of smooth muscle cells (SMCs) with the virus in vitro caused cholesterol accumulation.

Evidence was subsequently published extending the infection/atherosclerosis paradigm to humans. Thus, pathogens were found to reside in human atherosclerotic vessels,^5–8 and seroepidemiological studies demonstrated an association between pathogen-specific antibodies and atherosclerosis. Such associations were found with multiple pathogens, including cytomegalovirus (CMV), herpes . . . [Full Text of this Article]