# Role of collagen heterogeneity in remodeling of acute and chronic heart scars

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $507,000

## Abstract

Project Summary/Abstract
The mammalian heart possesses a poor ability to regenerate after ischemic cardiac injury and heals via scar
formation. Multiple clinical studies have demonstrated that the size of scar tissue is an independent predictor of
cardiovascular outcomes and mortality after acute myocardial infarction. However, little is understood about
factors that regulate the degree of fibrosis or size of scar tissue after acute ischemic cardiac injury. Collagens
are the most differentially upregulated genes following ischemic cardiac injury and remain the most abundant
form of extracellular matrix (ECM) proteins secreted in the infarcted heart. Type I and III collagens are the
principal collagens found in the heart but we show that a large number of collagens that are minimally
expressed in the uninjured heart are robustly induced following ischemic cardiac injury. In this proposal, we
investigate the physiological necessity of collagen heterogeneity and demonstrate that type V collagen, a
fibrillar collagen plays a critical role in regulating the size of scar tissue after ischemic cardiac injury. Using
multiplexing of RNA-FISH (fluorescence in situ hybridization) or MERFISH, we create a collagen map of the
heart and use genetic loss of function techniques to determine the functional significance of type V collagen in
regulating the size of post infarct scar tissue and heart function. We determine how the chemical composition
of ECM changes following type V collagen deletion, study the mechano-biological properties of altered matrix
and examine how such changes affect cardiac function and distribution of myocardial wall stress. We dissect
the molecular mechanisms mediating regulation of scar size by type V collagen. We demonstrate that type V
collagen deletion is associated with profound activation of cardiac fibroblasts in the infarcted heart and show
that augmented myofibroblast activation is secondary to an altered integrin expression profile on cardiac
fibroblasts. We study the mechanisms of altered integrin expression, integrin mediated mechanisms driving
myofibroblast activation and determine whether inhibition of specific integrins can rescue the phenotype of
increased post infarct scarring observed in type V collagen deficient states. Taken together, our proposal will
lead to a broader understanding of cardiac wound healing and illustrate a new paradigm of cardiac repair
where the structural constituents of heart scars regulate the size of scar itself.

## Key facts

- **NIH application ID:** 10202723
- **Project number:** 5R01HL149687-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Arjun Deb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $507,000
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202723

## Citation

> US National Institutes of Health, RePORTER application 10202723, Role of collagen heterogeneity in remodeling of acute and chronic heart scars (5R01HL149687-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10202723. Licensed CC0.

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