出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituentsof VLDL and HDL. ApoA-V counteracts the effect of apoC-III ontriglyceride (TG) metabolism with poorly defined mechanisms.To better understand the effects of apoA-V on TG and cholesterolmetabolism, we delivered apoA-V cDNA into livers of hypertriglyceridemicAPOC3 transgenic mice by adenovirus-mediated gene transfer.In response to hepatic apoA-V production, plasma TG levels werereduced significantly as a result of enhanced VLDL catabolismwithout alternations in VLDL production. This effect was associatedwith reduced apoC-III content in VLDL. Increased apoA-V productionalso resulted in decreased apoC-III and increased apoA-I contentin HDL. Furthermore, apoA-V-enriched HDL was associated withenhanced LCAT activity and increased cholesterol efflux. Thiseffect, along with apoE enrichment in HDL, contributed to HDLcore expansion and -HDL formation, accounting for significantincreases in both the number and size of HDL particles. As aresult, apoA-V-treated APOC3 transgenic mice exhibited decreasedVLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediatedreduction of apoC-III content in VLDL represents an importantmechanism by which apoA-V acts to ameliorate hypertriglyceridemiain adult APOC3 transgenic mice. In addition, increased apoA-Vlevels accounted for cholesterol redistribution from VLDL tolarger HDL particles. These data suggest that in addition toits TG-lowering effect, apoA-V plays a significant role in modulatingHDL maturation and cholesterol metabolism.Supplementary key words apolipoprotein A-V • apolipoprotein C-III • hypertriglyceridemia • lipoprotein metabolism • very low density lipoprotein • high density lipoprotein
Abbreviations: apoA-V, apolipoprotein A-V; LDLR, low density lipoprotein receptor; SR-BI, scavenger receptor class B type I; TG, triglyceride
-HDL formation, accounting for significant increases in both the number and size of HDL particles. As a result, apoA-V-treated APOC3 transgenic mice exhibited decreased VLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediated reduction of apoC-III content in VLDL represents an important mechanism by which apoA-V acts to ameliorate hypertriglyceridemia in adult APOC3 transgenic mice. In addition, increased apoA-V levels accounted for cholesterol redistribution from VLDL to larger HDL particles. These data suggest that in addition to its TG-lowering effect, apoA-V plays a significant role in modulating HDL maturation and cholesterol metabolism.
Supplementary key words apolipoprotein A-V • apolipoprotein C-III • hypertriglyceridemia • lipoprotein metabolism • very low density lipoprotein • high density lipoprotein
Abbreviations: apoA-V, apolipoprotein A-V; LDLR, low density lipoprotein receptor; SR-BI, scavenger receptor class B type I; TG, triglyceride
