ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency
Copyright policy )ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency
Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we investigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyceridemia. Here, we studied the role of LPL and two potent modifiers, the LPL inhibitor apoC-III and the LPL activator apoA-V, in APOE2-knockin (APOE2) mice. Injection of heparin in APOE2 mice reduced plasma TG by 53% and plasma total cholesterol (TC) by 18%. Adenovirus-mediated overexpression of LPL reduced plasma TG by 85% and TC by 40%. Both experiments indicate that the TG in apoE2-enriched particles is a suitable substrate for LPL. Indirect activation of LPL activity via deletion of Apoc3 in APOE2 mice did not affect plasma TG levels, whereas overexpression of Apoa5 in APOE2 mice did reduce plasma TG by 81% and plasma TC by 41%. In conclusion, the hypertriglyceridemia in APOE2 mice can be ameliorated by the direct activation of LPL activity. Indirect activation of LPL via overexpression of apoA-V does, whereas deletion of apoC-III does not, affect the plasma TGs in APOE2 mice. These data indicate that changes in apoA-V levels have a dominant effect over changes in apoC-III levels in the improvement of APOE2-associated hypertriglyceridemia.
- Boston College United States
- University of North Carolina at Chapel Hill United States
- Boston University United States
- Department of Human Genetics Switzerland
- Amsterdam UMC Netherlands
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Male, clusterin, Apolipoprotein E2, apolipoprotein C-III, cholesterol blood level, heparin, mouse mutant, stimulation, Biochemistry, apolipoprotein A5, Mice, apolipoprotein M, apolipoprotein B, Adenovirus, apolipoprotein C, animal, genetics, apolipoprotein A, gene transfer, apolipoprotein D, conference paper, apolipoprotein E, Hypertriglyceridemia, Mice, Knockout, Gene Transfer Techniques, Adenovirus-mediated gene transfer, APOE2-knockin mice, apolipoprotein E2, Lipids, Lipoprotein lipase-mediated very low density lipoprotein-triglyceride hydrolysis, beta2 glycoprotein 1, adenovirus-mediated gene transfer, female, gene overexpression, hypertriglyceridemia, animal experiment, apolipoprotein, Physiological Sciences, QD415-436, Adenoviridae, in vivo study, apolipoprotein A-V, apolipoprotein C3, blood, Animals, controlled study, mouse, Apolipoprotein C-III, nonhuman, lipoprotein lipase-mediated very low density lipoprotein-triglyceride hydrolysis, animal model, disease association, triacylglycerol blood level, Apoa5 protein, mouse, Lipoprotein Lipase, Apolipoproteins, Apolipoprotein A-V, physiology, lipoprotein deficiency
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