Intravenous injection of apolipoprotein A-V reconstituted high-density lipoprotein decreases hypertriglyceridemia in apoav-/- mice and requires glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1.
Intravenous injection of apolipoprotein A-V reconstituted high-density lipoprotein decreases hypertriglyceridemia in apoav-/- mice and requires glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1.
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DOI：
10.1161/atvbaha.110.210815
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Forte TM
中科院分区：
文献类型：
--
作者：
Shu X;Nelbach L;Weinstein MM;Burgess BL;Beckstead JA;Young SG;Ryan RO;Forte TM
Apolipoprotein A-V (apoA-V), a minor protein associated with lipoproteins, has a major effect on triacylglycerol (TG) metabolism. We investigated whether apoA-V complexed with phospholipid in the form of a reconstituted HDL (rHDL) has potential utility as a therapeutic agent for treatment of hypertriglyceridemia when delivered intravenously. Intravenous injection studies were performed in genetically engineered mouse models of severe hypertriglyceridemia including apoav-/- and gpihbp1-/- mice. Administration of apoA-V rHDL to hypertriglyceridemic apoav−/− mice resulted in a 60% reduction in plasma TG concentration after 4 h. This decline can be attributed to enhanced catabolism/clearance of VLDL where VLDL TG and cholesterol were reduced ∼60%. ApoA-V which associated with VLDL after injection was also rapidly cleared. Site-specific mutations in the heparin-binding region of apoA-V (amino acids 186-227) attenuated apoA-V rHDL TG-lowering activity by 50% suggesting this sequence element is required for optimal TG-lowering activity in vivo. Unlike apoav-/- mice, injection of apoA-V rHDL into gpihbp1-/- mice had no effect on plasma TG levels and apoA-V remained associated with plasma VLDL. Intravenously injected apoA-V rHDL significantly lowers plasma TG in an apoA-V deficient mouse model. Its intravenous administration may have therapeutic benefit in human subjects with severe HTG, especially in cases involving apoA-V variants associated with HTG.
