# Molecular Basis of Exercise-induced Changes in HDL Function

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2021 · $777,672

## Abstract

High-density lipoprotein (HDL) particles have multiple atheroprotective properties, including removal of excess
cholesterol from peripheral tissues, inhibition of vascular inflammation, and reduction of oxidative stress. It is
thought that HDL function is mediated by the molecules bound to HDL particles, which include proteins, lipids,
and microRNAs. HDL function and composition have been shown to be impaired in various disease states and
measures of HDL function are strong, independent predictors of cardiovascular disease risk. Recent work has
shown that exercise training improves HDL function in a dose-specific manner. Thus, the overall goal of the
proposed study is to examine the effects of exercise dose and type on HDL function and identify the clinical
and molecular factors underlying exercise-induced changes in HDL function. The proposed study will utilize
existing data and samples from four large, completed NIH-funded clinical exercise trials (N=1224) to test the
study hypotheses: HERITAGE Family Study (N=731; 5 mos, same aerobic dose in healthy adults), STRRIDE
AT/RT (N=144; 8 mos, aerobic, resistance, or combination training in overweight adults with mild dyslipidemia),
STRRIDE-PD (N=175; 6 mos, 4 groups differing in aerobic exercise amount and/or intensity in adults with pre-
diabetes), and HART-D study (N=174; 9 mos, time-matched aerobic, resistance, or combination training in
diabetics). Specifically, Aim 1 will examine how exercise amount, exercise intensity, and exercise type affect
three measures of HDL function (cholesterol efflux capacity, anti-inflammatory and anti-oxidant properties) and
whether the exercise effects on HDL function differ by race, sex, and/or metabolic profile (e.g., diabetes,
metabolic syndrome, obesity). Aim 2 will examine the effects of exercise training on the HDL proteome, HDL
lipidome, and HDL microRNA profiles and validate sex- and race-specific HDL molecular signatures that
predict exercise-induced changes in HDL function. Furthermore, Aim 2 will integrate the generated HDL
function and HDL composition data with available genomic, metabolomic, and muscle gene expression data to
identify novel genes, pathways, and networks associated with exercise-induced changes in HDL function. The
proposed research will determine the amount, intensity, and type of exercise that improves HDL function and
will identify specific groups of molecules underlying these functional changes. Identifying clinical and molecular
predictors of exercise-induced changes in HDL function could help provide targeted exercise programs tailored
to specific sex-race-disease groups to maximize the benefits.

## Key facts

- **NIH application ID:** 10144017
- **Project number:** 5R01HL146462-03
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Mark Andrew Sarzynski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,672
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144017

## Citation

> US National Institutes of Health, RePORTER application 10144017, Molecular Basis of Exercise-induced Changes in HDL Function (5R01HL146462-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144017. Licensed CC0.

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