# The Genetic and Molecular Basis of Cholesterol Efflux

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $703,119

## Abstract

Project Summary
Low high-density lipoprotein cholesterol (HDL-C) is a major risk factor for atherosclerotic
cardiovascular disease (ASCVD), the leading cause of death. However, strategies to improve
atheroprotection by raising HDL-C levels have failed to improve outcomes. Macrophage-
specific cholesterol efflux is the first critical step of reverse cholesterol transport, a key
atheroprotective pathway. Cholesterol efflux is inversely associated with incident ASCVD
events; however, the mechanisms that underlie variation in cholesterol efflux are unknown.
There is a critical need to identify factors that regulate cholesterol efflux to advance
understanding of the reverse cholesterol transport pathway, a biological process that has broad
implications across a variety of disease states including atherosclerosis. The overall objective of
this proposal is to systematically ascertain the genetic and molecular factors governing variation
in cholesterol efflux. We propose to carry out our objective by using two large, population-
based multi-ethnic cohorts, the Dallas Heart Study (DHS) and the Multi-Ethnic Study of
Atherosclerosis (MESA) to pursue the following aims: 1) determine the contribution of genetic
factors to inter-individual variability in cholesterol efflux and whether these factors are causally
associated with ASCVD; and 2) identify the metabolite and protein signature of cholesterol efflux
in a sex- and ethnicity-specific manner. We expect to characterize the genetic, metabolic, and
protein regulators of cholesterol efflux to support future studies targeting manipulation of the
reverse cholesterol transport pathway.

## Key facts

- **NIH application ID:** 10075304
- **Project number:** 5R01HL136724-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Anand Kumar Rohatgi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $703,119
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075304

## Citation

> US National Institutes of Health, RePORTER application 10075304, The Genetic and Molecular Basis of Cholesterol Efflux (5R01HL136724-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10075304. Licensed CC0.

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