# Genetic mapping of variable cardiac cell composition in the rat

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $208,896

## Abstract

PROJECT SUMMARY
The physiological response to cardiac injury such as myocardial infarction is highly variable in humans.
Emerging literature has identified several cardiac cell types that are thought to protect individuals from adverse
outcomes following injury, and even promote some degree of myocardial regeneration. Specifically, frequency
of mononuclear diploid cardiomyocytes in the steady state myocardium correlates with improved outcomes
following MI in the mouse model. Furthermore, emerging evidence demonstrates that cardiac resident
macrophage populations promote reparative healing in the context of cardiac injury. Importantly, each of these
cell types are present in the steady state heart prior to injury, are present at variable frequencies across
genetically inbred rodent strains, and are easily quantifiable. Thus, these easily quantifiable traits allow for
genome wide association studies (GWAS) to identify genes linked to resilience to cardiac injury and tissue
regeneration. Indeed, recent work across a collection of inbred mouse strains, the Hybrid Mouse Diversity
Panel (HMDP), achieved exactly this goal for heart regeneration. Here, we propose to expand this concept
recently implemented in a single cell type in the mouse to multiple cell types in the rat, which has several
advantages over the mouse. First, there are numerous situations where rat physiology more closely resembles
that of humans, suggesting this genetic model could be a more faithful pre-clinical model. Second, the
equivalent collection of inbred rats, known as the Hybrid Rat Diversity Panel (HRDP), is currently being
rederived here at our institution (Medical College of Wisconsin). Most importantly, the HRDP displays
substantially greater genetic diversity across the panel, but with the same mapping power as the mouse
equivalent, suggesting more loci can be mapped to the quantitative trait using the rat. Here, we propose to
perform GWAS-based mapping using the HRDP to identify candidate genes underlying the frequency of
mononuclear diploid cardiomyocytes (Aim 1) and frequency of tissue resident cardiac macrophages (Aim 2) in
the steady state heart. Both aims will test the effect of variable frequency of these two cell populations on
cardiac physiological homeostasis and resistance to myocardial infarction injury. Notably, mechanistic insights
resulting from genes identified here could be applied to advancing cardiac regeneration strategies, predicting
susceptibility to heart failure progression, and developing personalized treatments for heart failure patients.

## Key facts

- **NIH application ID:** 10458033
- **Project number:** 5R21HL156022-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Caitlin C O'Meara
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $208,896
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458033

## Citation

> US National Institutes of Health, RePORTER application 10458033, Genetic mapping of variable cardiac cell composition in the rat (5R21HL156022-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10458033. Licensed CC0.

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