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

Juraj Koska, Jeremy Furtado, Yueming Hu, Shripad Sinari, Matthew J. Budoff, Dean Billheimer, Dobrin Nedelkov, Robyn L. McClelland, Peter D. Reaven

Research output: Contribution to journalArticlepeer-review

Abstract

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 Americans (AA), Chinese Americans (CA), and Hispanics (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 Hispanics (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.

Original languageEnglish (US)
Pages (from-to)100263
Number of pages1
JournalJournal of Lipid Research
Volume63
Issue number9
DOIs
StatePublished - Sep 1 2022

Keywords

  • apolipoprotein posttranslational proteoforms
  • atherosclerosis
  • cholesterol
  • HDL
  • lipid metabolism
  • lipid transport
  • mass spectrometry
  • proteomics
  • race/ethnicity
  • triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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