The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma apoC-III proteoforms (by mass spectrometric immunoassay) and plasma lipids were tested in two randomized clinical trials: ACT NOW, a study of pioglitazone in subjects with impaired glucose tolerance (n = 531), and RACED (n = 296), a study of intensive glycemic control and atherosclerosis in type 2 diabetes patients. At baseline, higher relative apoC-(I)II2 and apoC-III2/apoC-III1 ratios were associated with lower triglycerides and total cholesterol in both cohorts, and with lower small dense LDL in the RACED. Longitudinally, changes in apoC-III2/apoC-III1 were inversely associated with changes in triglycerides in both cohorts, and with total and small dense LDL in the RACED. apoC-III2/apoC-III1 was also higher in patients treated with PPAR-gamma agonists and was associated with reduced cardiovascular events in the RACED control group. Ex vivo studies of apoC-III complexes with higher apoC-III2/apoC-III1 showed attenuated inhibition of VLDL uptake by HepG2 cells and LPL-mediated lipolysis, providing possible functional explanations for the inverse association between a higher apoC-III2/apoC-III1 and hypertriglyceridemia, proatherogenic plasma lipid profiles, and cardiovascular risk.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/614755 |
| Date | 05 1900 |
| Creators | Koska, Juraj, Yassine, Hussein, Trenchevska, Olgica, Sinari, Shripad, Schwenke, Dawn C., Yen, Frances T., Billheimer, Dean, Nelson, Randall W., Nedelkov, Dobrin, Reaven, Peter D. |
| Contributors | Univ Arizona |
| Publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | Copyright © 2016 American Society for Biochemistry and Molecular Biology |
| Relation | http://www.jlr.org/lookup/doi/10.1194/jlr.P064816, http://www.jlr.org/content/suppl/2016/03/03/jlr.P064816.DC1.html |
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