# The role of pericytes in scar formation following stroke and myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $427,080

## Abstract

Stroke and myocardial infarction (MI) are ischemic diseases that are leading causes of mortality and morbidity.
Due to the limited regenerative capacity of the brain and the heart, injury leads to irreversible loss of neurons
and cardiomyocytes, with subsequent scar formation. The process of scar formation is highlighted by excess
deposition of extracellular matrix proteins which blocks tissue repair and prevents functional recovery in the brain
and the heart. In the brain, recent evidence indicates that the traditional concepts of astrocytes forming scar may
be incorrect. In the heart, there may be a key role for other mesenchymal cells in scar formation in addition to
cardiac fibroblasts.
Pericytes are a heterogeneous population of mural cells located on the abluminal surface of the
microvasculature, where they communicate with endothelial cells by means of physical contact and paracrine
signaling. Recent studies and work from our laboratories have suggested that pericytes may contribute to fibrosis
after an ischemic injury by migration to the site of injury, where they contribute to collagen deposition. We have
demonstrated expression of common genes in pericytes in both organ systems with similar migratory patterns
to site of injury, suggestive of parallel pathways that regulate pericyte activation in the brain and the heart. This
data suggests that pericytes are a scar-forming cell population that may be a target for modulating the balance
between tissue fibrosis and repair. However, detailed study of pericytes has been hampered by lack of markers
that hinder their isolation and the ability for targeting of key molecular pathways that may drive scar formation.
Furthermore, it is not entirely clear whether the heterogeneous pericyte populations possess distinct functional
roles, such that a subpopulation is responsive to and participates in fibrosis after injury. This grant brings together
neuroscience and cardiovascular expertise to develop a novel platform for studying how pericytes may actively
contribute to the fibrotic scar in the two most common and devastating adult ischemic diseases.
We hypothesize that pericytes contain distinct subpopulations that preferentially localize to the site of ischemic
injury and directly participate in scar formation. In specific aim 1, we will use novel lineage-tracing techniques
to investigate proliferation and migration of pericytes to the site of injury and examine their participation in scar
formation. In specific aim 2, we will perform single-cell gene expression profiling of brain and heart pericytes
before and after injury to map the transcriptional changes of pericytes as they become pro-fibrotic. In specific
aim 3, we will determine the molecular mechanisms that regulate pericyte activation by performing gain and loss
of function using in vitro and in vivo models. Supported by our preliminary data, the proposed project addresses
an important issue of how pericytes participate in the development a...

## Key facts

- **NIH application ID:** 10769764
- **Project number:** 5R01NS112256-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Stanley Thomas Carmichael
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,080
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769764

## Citation

> US National Institutes of Health, RePORTER application 10769764, The role of pericytes in scar formation following stroke and myocardial infarction (5R01NS112256-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10769764. Licensed CC0.

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