ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency
| Autor: | Caroline C. van der Hoogt, Ko Willems van Dijk, Kyriakos E. Kypreos, Albert K. Groen, Nobuyo Maeda, Patrick C.N. Rensen, Gery Gerritsen, Frank G. Schaap, Louis M. Havekes, Peter J. Voshol |
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| Přispěvatelé: | Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Medical Biochemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Very low-density lipoprotein Apolipoprotein C Apolipoprotein B apolipoprotein C-III QD415-436 Biology Biochemistry Adenoviridae apolipoprotein A-V Mice Endocrinology Internal medicine Hyperlipidemia medicine Animals Hypertriglyceridemia Mice Knockout Lipoprotein lipase lipoprotein lipase-mediated very low density lipoprotein-triglyceride hydrolysis digestive oral and skin physiology Gene Transfer Techniques APOE2-knockin mice nutritional and metabolic diseases apolipoprotein E2 Cell Biology medicine.disease Lipids adenovirus-mediated gene transfer Lipoprotein Lipase Apolipoproteins biology.protein Apolipoprotein C3 lipids (amino acids peptides and proteins) Research Article |
| Zdroj: | Journal of Lipid Research, Vol 49, Iss 5, Pp 1048-1055 (2008) Journal of lipid research, 49(5), 1048-1055. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0022-2275 |
| DOI: | 10.17615/spxd-r112 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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