Apolipoproteins (apo) C1 and C2 are small interchangeable molecules that regulate lipoprotein metabolism. ApoC1 inhibits lipoprotein lipase (LPL) and stimulates reverse cholesterol transport while apoC2 activates LPL. Both exist as full-size native and minor truncated proteoforms; however, whether distribution of these apoC1 and C2 proteoforms may influence plasma lipids is largely unknown. Baseline plasma from 5,791 MESA participants was tested for truncated to native apoC1 and apoC2 ratios (apoC1’/C1; apoC2’/C2) . Total apoC1 and C2 concentrations were measured in a subset of 3,851 participants. Plasma lipids were measured for up to 6 times over 15 years. In adjusted models (Table) , higher apoC1’/C1 was associated with lower triglycerides (TG) and higher total (TC) and LDL cholesterol both at baseline and follow-up, and higher HDL at follow-up. Higher apoC2’/C2 was associated with lower TG and higher LDL at baseline, and higher baseline and follow-up TC and HDL. In contrast, the associations of total apoC1 and apoC2 concentrations with TG and HDL were largely in opposite directions of their proteoform ratios. For example, plasma TG were inversely associated with apoC1 and apoC2 truncation but positively associated with total apoC1 and apoC2 concentrations. Our data indicate a possible role of posttranslational apoC1 and apoC2 modification in regulating lipid metabolism.
J.Koska: None. J.Furtado: Research Support; Eli Lilly and Company, Pfizer Inc. S.Sinari: None. R.Mcclelland: None. D.Billheimer: None. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc.
National Institutes of Health (R01-HL138969