Plasma proteoforms of apolipoproteins C-I and C-II are associated with plasma lipids in the Multi-Ethnic Study of Atherosclerosis

• Published in: Journal of lipid research Vol. 63; no. 9; p. 100263
• Main Authors: Koska, Juraj, Furtado, Jeremy, Hu, Yueming, Sinari, Shripad, Budoff, Matthew J., Billheimer, Dean, Nedelkov, Dobrin, McClelland, Robyn L., Reaven, Peter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2022; Elsevier
• Subjects: Apolipoprotein C-II; Apolipoprotein C-III; apolipoprotein posttranslational proteoforms; Apolipoproteins; Atherosclerosis; cholesterol; Female; HDL; Humans; lipid metabolism; lipid transport; mass spectrometry; proteomics; race/ethnicity; Triglycerides; atherosclerosis; AA; MESA; proteomics; lipid metabolism; lipid transport; DPP-4; LPL; triglycerides; race/ethnicity; TRL; HDL; GFR; cholesterol; mass spectrometry; apolipoprotein posttranslational proteoforms; apoC-I; apoC-II; CA
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1016/j.jlr.2022.100263

Apolipoproteins (apo) C-I and C-II are key regulators of triglyceride and HDL metabolism. Both exist as full-size native and truncated (apoC-I'; apoC-II') posttranslational proteoforms. However, the determinants and the role of these proteoforms in lipid metabolism are unknown. Here, we measured apoC-I and apoC-II proteoforms by mass spectrometry immunoassay in baseline and 10-year follow-up plasma samples from the Multi-Ethnic Study of Atherosclerosis. We found that baseline total apoC-I (mean = 9.2 mg/dl) was lower in African American (AA), Chinese American (CA), and Hispanic American (by 1.8; 1.0; 1.0 mg/dl vs. whites), higher in women (by 1.2 mg/dl), and positively associated with plasma triglycerides and HDL. Furthermore, we observed that the truncated-to-native apoC-I ratio (apoC-I'/C-I) was lower in CA, negatively associated with triglycerides, and positively associated with HDL. We determined that total apoC-II (8.8 mg/dl) was lower in AA (by 0.8 mg/dl) and higher in CA and Hispanic American (by 0.5 and 0.4 mg/dl), positively associated with triglycerides, and negatively associated with HDL. In addition, apoC-II'/C-II was higher in AA and women, negatively associated with triglycerides, and positively associated with HDL. We showed that the change in triglycerides was positively associated with changes in total apoC-I and apoC-II and negatively associated with changes in apoC-I'/C-I and apoC-II'/C-II, whereas the change in HDL was positively associated with changes in total apoC-I and apoC-II'/C-II and negatively associated with change in total apoC-II. This study documents racial/ethnic variation in apoC-I and apoC-II plasma levels and highlights apolipoprotein posttranslational modification as a potential regulator of plasma lipids.