Chlamydia pneumoniae accelerates coronary artery disease progression in transgenic hyperlipidemia-genetic hypertension rat model.
Chlamydia pneumoniae (Cpn) has been associated with human coronary artery disease but causal relevance as a risk factor has not been shown. Several rabbit and mouse model studies demonstrate exacerbation of aortic atherosclerosis by Cpn, however impact of Cpn on coronary artery disease (CAD) and survival outcomes has not been shown. To study this, we used specific pathogen-free, inbred, transgenic-CAD Dahl salt-sensitive (S) hypertensive (Tg53) rats and control inbred, non-transgenic Dahl S (nonTg) rats to analyze the effects of Cpn infection on macrophage foam cell formation, coronary artery disease progression, and effect on survival. Cpn infection induced acceleration of foam cell formation in hyperlipidemic Tg53 recruited peritoneal macrophages. This effect is hyperlipidemia-dependent. The transcription profile of Tg53-Cpn macrophage foam cells is different from control mock-inoculated (Tg53-spg) and heat-inactivated (Tg53-iCpn) macrophages (ANOVA P < 0.0001). Decreased survival was detected in Tg53-Cpn compared with control nonTg-Cpn and mock-infected Tg53-mouse pneumonitic rats (P = 0.009) and was associated with "culprit" coronary plaques and left atrial thrombi. These data demonstrate that in the presence of significant hyperlipidemia and hypertension, one-time Cpn infection at 5 mo of age (associated with early CAD stage) accelerates progression to overt-CAD in the Tg53 rat model. The data support the hypothesis that untreated Cpn infection is a causal risk factor for CAD progression most likely mediated by Cpn-induced accelerated macrophage foam cell formation.
Herrera
Victoria L M
VL
Section of Molecular Medicine and Molecular Genetics, Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA. vherrera@bu.edu
Shen
Li
L
Lopez
Lyle V
LV
Didishvili
Tamara
T
Zhang
You-Xun
YX
Ruiz-Opazo
Nelson
N
D000818:Animals; D030801:Animals, Genetically Modified; D023521:Chlamydophila Infections / Q000378:metabolism*; D016993:Chlamydophila pneumoniae / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism*; D004195:Disease Models, Animal; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010537:Peritoneum / Q000378:metabolism; D051381:Rats