# Genetic modifiers of atherosclerosis and macrophage phenotypes

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $632,638

## Abstract

Summary
Heart disease is the number one killer of men and women in the United States. Although the
incidence of cardiovascular disease deaths has declined, it still accounts for ~1 out of every 3
deaths. Coronary artery disease (CAD) due to atherosclerosis was responsible for most of these
deaths. Despite increased knowledge about CAD risk factors and the availably of drugs to treat
them, the CAD problem has not been solved. Large human genome wide association studies
have identified many common genetic variants associated with CAD, but only a small fraction of
the heritable risk has been discovered. This proposal aims to perform mouse genetic and
genomic studies to identify atherosclerosis modifier genes and genetic modifiers of macrophage
foam cell lipid droplet metabolism and inflammation, yielding insights into the mechanisms that
regulate these pathways. The first aim of the proposed studies involves identifying the
responsible genes and genetic variation that give rise to in vitro macrophage phenotypes using
sophisticated genetic and gene editing approaches. The second aim of the proposed studies is
to identify the mouse atherosclerosis modifier gene in a genetic locus identified on chromosome
2. This aim will use sophisticated gene editing as well as a newer mouse model of
atherosclerosis induced by treatment with an antisense oligonucleotide targeting the low density
lipoprotein receptor. These findings may lead to novel drug targets and therapies to prevent or
treat CAD. The relevance of the proposed studies is that they address a significant health
concern, coronary artery disease, and will yield insight into the mechanisms that modify
atherosclerosis susceptibility. The discovery of novel pathways and proteins that regulate
atherosclerosis and foam cell cholesterol metabolism and inflammation offers hope for new
modes of risk assessment, prevention, and therapy.

## Key facts

- **NIH application ID:** 10306932
- **Project number:** 1R01HL156499-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Jonathan D Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $632,638
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10306932

## Citation

> US National Institutes of Health, RePORTER application 10306932, Genetic modifiers of atherosclerosis and macrophage phenotypes (1R01HL156499-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10306932. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*