# Apolipoprotein-C Proteoforms in Dyslipidemia and Cardiovascular Disease

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $397,100

## Abstract

Abstract
Apolipoprotein C-III (apoC-III) is increasingly recognized as an important determinant of dyslipidemia and
cardiovascular risk. Although apoC-III is typically measured as total plasma apoC-III concentration, it is
present in blood in several post-translational proteoforms - with the most abundant forms containing zero,
one or two sialic acid molecules. However, the relationships between apoC-III proteoforms and patterns of
dyslipidemia, atherosclerosis and cardiovascular disease (CVD) risk are largely unknown. We found that
higher relative amounts of apoC-III with two sialic acids (but not 0 or 1) were linked in cross-sectional
and prospective studies with lower triglyceride levels, and were associated with reduced risk for CVD
events. Our data also indicate ratios of these proteoforms may vary with race and lipid-lowering therapies and
that proteoforms of both apoC-I and C-II also demonstrate unique relationships with blood lipid concentrations.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a large community based cohort study of CVD risk
factors, subclinical measures of atherosclerosis and determinants of major CVD events. Importantly, the
diverse ethnic and racial population within the study will permit a definitive study of these proteoforms and their
relationships with lipid abnormalities, atherosclerosis and CVD events while exploring ethnic/racial differences.
The present proposal will utilize a novel mass spectrometry immunoassay (MSIA) to investigate the
relationships of apoC-III (and secondarily apo-CI and C-II) proteoforms with plasma lipid concentrations,
progression of vascular calcification and carotid atherosclerosis, and development of major adverse
cardiovascular events (MACE) within the MESA cohort. Total plasma apoC-III concentrations and apoC-III
relative proteoform amounts will be determined by MSIA in baseline and 10-year follow-up plasma samples.
Aim 1 will examine the cross-sectional and longitudinal associations between apoC-III measures and plasma
lipids. Aim 2 will determine whether apoC-III measures predict baseline atherosclerosis and atherosclerosis
progression evaluated from CT scans of coronary arteries and ultrasonography-derived carotid-intima-media
thickness measured during MESA. Aim 3 will determine the relationship between apoC-III measures and
incident MACE and total CVD events.
This will be the first large study evaluating relationships between apoC proteoforms and CVD risk. As
therapies are now being developed to specifically target apoC proteins to reduce triglycerides and CVD risk, a
more definitive understanding of the complexity and clinical implications of the apoC family of proteins is
needed. As diabetes and lipid-lowering therapies appear to have differential effects on apoC proteoforms,
targeting therapy to specific proteoforms and/or subsets of individuals may be beneficial. As we have
demonstrated that there are proteoforms of many other plasma proteins, this study may also help hi...

## Key facts

- **NIH application ID:** 10180579
- **Project number:** 3R01HL138969-04S1
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Peter D Reaven
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,100
- **Award type:** 3
- **Project period:** 2018-12-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180579

## Citation

> US National Institutes of Health, RePORTER application 10180579, Apolipoprotein-C Proteoforms in Dyslipidemia and Cardiovascular Disease (3R01HL138969-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180579. Licensed CC0.

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