# Vascular smooth muscle cell heterogeneity and disease

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $831,140

## Abstract

Project Summary
 Vascular cell heterogeneity is a fascinating but poorly understood phenomenon. Numerous vascular cell
types undergo fate transitions under pathological conditions. This includes endothelial cells (ECs) undergoing
endothelial-to-mesenchymal transition (EndMT) and acquiring certain characteristics typical of macrophages
and smooth muscle cells (SMCs). SMCs, in turn, can also acquire macrophage-like features while bone
marrow-derived mononuclear cells can express certain EC and SMC markers when present at sites of chronic
inflammation. These cells fate transitions have been linked to various pathologies including atherosclerosis,
aneurysms, pulmonary hypertension and cavernous cerebral malformations. While the existence of these cell
fate transitions is now well accepted, little is known about the origin and characteristics of SMCs undergoing
these fate changes. Our preliminary data suggest that certain subpopulations of normal SMCs are particularly
prone to phenotypic modulation and are predominately pathogenic. We hypothesize that a small subpopulation
of normal SMCs is responsible for pathogenesis of CV diseases associated with expansion of the SMC pool
and that targeting these cells might prove to be a better and more specific therapeutic approach. It is our goal
in this application to define these cell populations, determine what drives their pathogenic responses and begin
identifying therapeutic approaches to controlling CV illnesses driven by specifically targeting these SMC
subsets.

## Key facts

- **NIH application ID:** 10559596
- **Project number:** 5R01HL152197-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Simons
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $831,140
- **Award type:** 5
- **Project period:** 2021-03-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10559596

## Citation

> US National Institutes of Health, RePORTER application 10559596, Vascular smooth muscle cell heterogeneity and disease (5R01HL152197-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10559596. Licensed CC0.

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