# Innate-like CD8+ T-cells facilitate in cardiac remodeling post-MI

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2024 · —

## Abstract

Regional myocardial ischemia that leads to injury and myocyte necrosis results in focal scar formation and a
reduction in ventricular systolic function. The constitutive properties of the infarcted myocardium are major
determinants of left ventricular remodeling. The long-term goal of the proposal is to investigate the mechanisms
of cardiac healing and scar composition after myocardial infarction (MI) to provide targets and novel pathways
that drive adverse cardiac remodeling and left ventricular dysfunction. The specific objective is to characterize
the physiological effects of a specialized CD8+ T-cell population termed the innate-like CD8+ T-cells (ILTs) and
dissect how these cells regulate cardiac scar composition and biomechanics after MI. The central hypothesis is
that ILTs decrease (ECM) deposition and alter fibroblast activity via granzyme K (GzmK)-mediated paracrine
signaling through protease activated receptor-1 (PAR1) leading to a less stiff scar. Aim 1 will test the
hypothesis that ILTs are a fundamental determinant of the constitutive properties of ischemia induced
myocardial scar and resulting changes in ventricular structure and function. Aim 2 will test the hypothesis that
one mechanism by which ILTs influence scar biomechanics and LV remodeling is GzmK induced alterations in
ECM degradation. Aim 3 will test the hypothesis that one mechanism by which ILTs inhibit fibroblast activation
is through GzmK induced PAR1 signaling. Our proposed research targets a novel cellular, molecular
mechanism that alters scar properties. Understanding this mechanism behind ILT-mediated effects on
constitutive properties of ischemia induced myocardial scar will provide targets and novel pathways that drive
adverse cardiac remodeling and LV dysfunction. The proposed study aligns with the mission of the VA
healthcare system by providing molecular knowledge to clinical practices so that we can continue to provide
exceptional health care that improves veteran health and well-being.

## Key facts

- **NIH application ID:** 10852893
- **Project number:** 5I01BX005848-02
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Kristine Y DeLeon-Pennell
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852893

## Citation

> US National Institutes of Health, RePORTER application 10852893, Innate-like CD8+ T-cells facilitate in cardiac remodeling post-MI (5I01BX005848-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10852893. Licensed CC0.

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