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Papers In Press, published online ahead of print April 16, 2007
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Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
Corresponding Author: dongh{at}pitt.edu
Apolipoproteins A-V and C-III are exchangeable constituents of VLDL and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride metabolism with poorly defined mechanisms. To better understand the effects of apoA-V on triglyceride and cholesterol metabolism, we delivered apoA-V cDNA into livers of hypertriglyceridemic APOC3 transgenic mice by adenovirus-mediated gene transfer. In response to hepatic apoA-V production, plasma triglyceride levels was significantly reduced, due to enhanced VLDL catabolism without alternations in VLDL production. This effect was associated with reduced apoC-III content in VLDL. Elevated apoA-V production also resulted in decreased apoC-III and increased apoA-I content in HDL. Furthermore, ApoA-V-enriched HDL was associated with enhanced LCAT activity and increased cholesterol efflux. This effect, along with apoE enrichment in HDL, contributed to HDL core expansion and alpha-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, elevated apoA-V levels accounted for cholesterol redistribution from VLDL to larger-sized HDL particles. These data suggest that in addition to its triglyceride-lowering effect, apoA-V plays a significant role in modulating HDL maturation and cholesterol metabolism.
Revised on March 6, 2007
Accepted on April 16, 2007
Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice
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