# Biomimetic nanomaterials for the immunomodulation of the cardiosplenic axis post-myocardial infarction

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $741,890

## Abstract

PROJECT SUMMARY/ABSTRACT
The healing response within the myocardium after a myocardial infarction (MI) is complex and involves both
temporal and regional changes including inflammation, cardiac scar formation, and tissue remodeling. Within
minutes following ischemic injury neutrophils and monocytes are recruited to the damaged heart. As the
monocytes are activated, enter the myocardium and are stimulated by the cardiac environment, they mature into
a diverse population of macrophages. In the first days post-MI, inflammatory monocytes and macrophages
facilitate the removal of necrotic tissue by secreting proteases and inflammatory enzymes and cytokines. As
healing progresses, the reparative less inflammatory macrophages begin to dominate, secreting anti-
inflammatory cytokines and communicating with myofibroblasts, endothelial cells, parenchymal and local
progenitor cells to help coordinate remodeling and repair of the damaged tissue. Over the last decade the
importance of the spleen has been highlighted as a reservoir for the majority of monocytes trafficking to the heart
in response to ischemic damage. Upon infarction, increased angiotensin II levels promote the migration of
monocytes from the spleen to the heart where they differentiate into macrophages and partake in the
inflammatory phase of the insult. Further, the spleen is a major site of monocyte proliferation post MI and
contributes significate numbers or monocytes throughout the duration of acute inflammation. Days after the initial
injury, the phenotype of monocytes recruited from the spleen changes to one that is reparative, differentiating
into macrophages which suppress inflammation, inducing matrix deposition and angiogenesis. We have
demonstrated that the systemic inhibition of HDACs results in myocardial preservation after MI, and more
recently shown that the delivery of this pan-HDAC inhibitor specifically to the spleen is capable of producing a
comparable therapeutic effect, yet at a 33-fold reduced dose. This proposal thus aims to unearth the
mechanisms responsible for this observed efficacy, both within the spleen and the heart. As well, the advanced
nanomaterials with enhanced splenic retention will also be utilized to dissect the relevant contributions of each
HDAC to the therapeutic effect, ultimately resulting in an optimized therapeutic regime.

## Key facts

- **NIH application ID:** 10981480
- **Project number:** 1R01HL170060-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** JASON R. McCARTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $741,890
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981480

## Citation

> US National Institutes of Health, RePORTER application 10981480, Biomimetic nanomaterials for the immunomodulation of the cardiosplenic axis post-myocardial infarction (1R01HL170060-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10981480. Licensed CC0.

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