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Título: | Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice |
Autor: | Qu, Shen; Perdomo, Germán CSIC ORCID CVN; Su, Dongming; D'Souza, Fiona M.; Shachter, Neil S. S; Dong, H. Henry | Palabras clave: | Apolipoprotein A-V Apolipoprotein C-III Hypertriglyceridemia Lipoprotein metabolism Very low density lipoprotein High density lipoprotein |
Fecha de publicación: | jul-2007 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | The Journal of Lipid Research 48: 1476-1487 (2007) | Resumen: | Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituents of VLDL and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride (TG) metabolism with poorly defined mechanisms. To better understand the effects of apoA-V on TG 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 TG levels were reduced significantly as a result of enhanced VLDL catabolism without alternations in VLDL production. This effect was associated with reduced apoC-III content in VLDL. Increased 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 α-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. | Versión del editor: | http://dx.doi.org/10.1194/jlr.M600498-JLR200 | URI: | http://hdl.handle.net/10261/222352 | DOI: | 10.1194/jlr.M600498-JLR200 | ISSN: | 0022-2275 | E-ISSN: | 1539-7262 |
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