Affiliation:
1. Molecular Genetics, Whitaker Cardiovascular Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, 715 Albany Street W509, Boston, MA 02118, U.S.A.
Abstract
We have investigated the ability of apoE (apolipoprotein E) to participate in the biogenesis of HDL (high-density lipoprotein) particles in vivo using adenovirus-mediated gene transfer in apoA-I−/− (apolipoprotein A-I) or ABCA1−/− (ATP-binding cassette A1) mice. Infection of apoA-I−/− mice with 2×109 pfu (plaque-forming units) of an apoE4-expressing adenovirus increased both HDL and the triacylglycerol-rich VLDL (very-low-density lipoprotein)/IDL (intermediate-density lipoprotein)/LDL (low-density lipoprotein) fraction and generated discoidal HDL particles. ABCA1−/− mice treated similarly failed to form HDL particles, suggesting that ABCA1 is essential for the generation of apoE-containing HDL. Combined infection of apoA-I−/− mice with a mixture of adenoviruses expressing both apoE4 (2×109 pfu) and human LCAT (lecithin:cholesterol acyltransferase) (5×108 pfu) cleared the triacylglycerol-rich lipoproteins, increased HDL and converted the discoidal HDL into spherical HDL. Similarly, co-infection of apoE−/− mice with apoE4 and human LCAT corrected the hypercholesterolaemia and generated spherical particles, suggesting that LCAT is essential for the maturation of apoE-containing HDL. Overall, the findings indicate that apoE has a dual functionality. In addition to its documented functions in the clearance of triacylglycerol-rich lipoproteins, it participates in the biogenesis of HDL-sized apoE-containing particles. HDL particles generated by this pathway may account at least for some of the atheroprotective functions of apoE.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
79 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献