| First Author | Westerterp M | Year | 2007 |
| Journal | Circulation | Volume | 116 |
| Issue | 19 | Pages | 2173-81 |
| PubMed ID | 17967778 | Mgi Jnum | J:142992 |
| Mgi Id | MGI:3822618 | Doi | 10.1161/CIRCULATIONAHA.107.693382 |
| Citation | Westerterp M, et al. (2007) Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice. Circulation 116(19):2173-81 |
| abstractText | 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 microg) 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. |
