Infection With Chlamydia pneumoniae Accelerates the Development of Atherosclerosis and Treatment With Azithromycin Prevents It in a Rabbit Model

作者：Joseph Brent Muhlestein, Jeffrey L. Anderson, Elizabeth H. Hammond, Liping Zhao, Sanjeev Trehan, Eric P. Schwobe, John F. Carlquist · 发表于：Circulation · 年份：1998 · DOI：10.1161/01.cir.97.7.633 · 被引用次数：519 · 研究领域：Reproductive tract infections research、Gut microbiota and health、Pneumonia and Respiratory Infections

BACKGROUND: Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model. METHODS AND RESULTS: Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount (0.25%) of cholesterol. Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin or no therapy. Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis. Vascular chlamydial antigen was assessed by direct immunofluorescence. MIT differed among treatment groups (P=.009), showing an increase in infected rabbits (0.55 mm; SE = 0.15 mm) compared with uninfected controls (0.16 mm; SE = 0.06 mm) and with infected rabbits receiving antibiotics (0.20 mm; SE = 0.03 mm) (both P<.025), whereas MIT in infected/treated versus control rabbits did not differ. PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern. Chlamydial antigen was detected in 2 untreated, 3 treated, and 0 control animals. CONCLUSIONS: Intranasal C...