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 μg) 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-α 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.

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