Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice

Article

关键词: HIGH-DENSITY-LIPOPROTEIN;    TOLL-LIKE RECEPTOR-4;    SERUM-AMYLOID-A;    CHLAMYDIA-PNEUMONIAE;    AGGRAVATES ATHEROSCLEROSIS;    ENDOTOXIN;    LESIONS;    INFLAMMATION;    DISEASE;    ATHEROGENESIS;   

DOI  :  10.1161/CIRCULATIONAHA.107.693382

来源: SCIE

【 摘 要 】

Background - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice. Methods and Results - Twelve-week-old apoe(-/-) apoc1(-/-) and apoe(-/-) apoc1(-/-) mice received weekly intraperitoneal injections of LPS (50 mu g) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe(-/-) apoc1(-/-) mice but increased it in apoe(-/-) apoc1(-/-) mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P < 0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-alpha response by macrophages in vitro. Conclusions - We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in apoe(-/-) mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.

【 授权许可】

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