| Autor: |
Herrera, Victoria L. M., Shen, Li, Lopez, Lyle V., Didishvili, Tamara, Zhang, You-Xun, Ruiz-Opazo, Nelson |
| Zdroj: |
Molecular Medicine; May 2003, Vol. 9 Issue: 5-8 p135-142, 8p |
| Abstrakt: |
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 Cpnon 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 Cpninfection on macrophage foam cell formation, coronary artery disease progression, and effect on survival. Cpninfection induced acceleration of foam cell formation in hyperlipidemic Tg53 recruited peritoneal macrophages. This effect is hyperlipidemia-dependent. The transcription profile of Tg53-Cpnmacrophage 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-Cpncompared with control nonTg-Cpnand 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 Cpninfection 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 Cpninfection is a causal risk factor for CAD progression most likely mediated by Cpn-induced accelerated macrophage foam cell formation. |
| Databáze: |
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