Human ApoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and cholesteryl ester transfer protein in transgenic mice.
AUTOR(ES)
Zhong, S
RESUMO
The plasma cholesteryl ester transfer protein (CETP) mediates the exchange of HDL cholesteryl esters with triglycerides of other lipoproteins. Subsequent lipolysis of the triglyceride-enriched HDL by hepatic lipase leads to reductions of HDL size and apoA-I content. To investigate a possible modulation of the effects of CETP by apoA-II, human CETP transgenic mice were cross-bred with transgenic mice expressing human apoA-II and, in some cases, human apoA-I and apoC-III (with human-like HDL and hypertriglyceridemia). CETP expression resulted in reductions of HDL and increases in VLDL cholesteryl ester in mice expressing human apoA-II, alone or in combination with apoA-I and apoC-III, indicating that apoA-II does not inhibit the cholesteryl ester transfer activity of CETP. However, CETP expression resulted in more prominent increases in HDL triglyceride in mice expressing both apoA-II and CETP, especially in CETP/apoA-II/apoAI-CIII transgenic mice. CETP expression caused dramatic reductions in HDL size and apoA-I content in apoAI-CIII transgenic mice, but not in apoA-II/AI-CIII transgenic mice. HDL prepared from mice of various genotypes showed inhibition of emulsion-based hepatic lipase activity in proportion to the apoA-II/apoA-I ratio of HDL. The presence of human apoA-II also inhibited mouse plasma hepatic lipase activity on HDL triglyceride. Thus, apoA-II does not inhibit the lipid transfer activity of CETP in vivo. However, coexpression of apoA-II with CETP results in HDL particles that are more triglyceride enriched and resistant to reductions in size and apoA-I content, reflecting inhibition of hepatic lipase by apoA-II. The inhibition of HDL remodeling by apoA-II could explain the relatively constant levels of HDL containing both apoA-I and apoA-II in human populations.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=330078Documentos Relacionados
- Hypertriglyceridemia and cholesteryl ester transfer protein interact to dramatically alter high density lipoprotein levels, particle sizes, and metabolism. Studies in transgenic mice.
- Dietary cholesterol increases transcription of the human cholesteryl ester transfer protein gene in transgenic mice. Dependence on natural flanking sequences.
- Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.
- Decreased cholesteryl ester transfer protein (CETP) mRNA and protein and increased high density lipoprotein following lipopolysaccharide administration in human CETP transgenic mice.
- Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism