# Microstructural Cues for the Treatment of Heart Failure

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $397,590

## Abstract

Project Summary/Abstract
Acute myocardial infarction (MI) is complicated by the subsequent development of scar tissue leading to
chronic cardiac insufficiency. Unfortunately, the lack of treatments for this maladaptive fibrotic response often
leads to a poor prognosis. Early attempts at stem cell delivery and biological therapeutics to address this
problem have been promising, but inconsistent. To meet this challenge, the Desai lab, with collaborators, has
developed a unique system of randomly dispersed polymeric microstructures, termed microrods, that have
been found to decrease fibroblast proliferation and promote cardiomyocyte hypertrophy in vitro. The objective
of this proposal is to study the mechanisms of interaction between microrods and cardiac fibroblasts in vitro
and in an animal models of infarct. We will also examine the effect of microstructures on cardiac remodeling.
This will enable the design of more effective therapies to prevent the development of cardiac scar tissue and
encourage recovery of heart function after MI. Based on previous studies and recent research on the
mechanical microenvironment, it is hypothesized that primary adult ventricular fibroblasts will respond to the
presence of microrods with a unique set of transcriptional changes in pathways relevant to
mechanotransduction, micro-environmental interaction, and extracellular matrix (ECM) deposition. In Aim 1,
quantitative analyses of changes in gene expression and immunofluorescence microscopy will be used to
examine cellular interactions with microrods in 3D culture. Specifically, quantification of ECM down-regulation
and mechanotransductive interactions will elucidate the mechanisms of effect of microstructures on fibroblasts.
In addition, HepIII conjugated microrods will be developed in order to augment vascularization, another key
element of cardiac regeneration. Aim 2 will use quantitative biochemical and immunohistochemical techniques
in an established rat model of MI to test the hypothesis that microrod injection into the infarct zone will produce
similar transcriptional changes in markers of the fibrotic response as seen in vitro through interaction with the
cardiac fibroblast population, as well as angiogenesis produced with the addition of HepIII to the microrods.
Finally, Aim 3 will evaluate the therapeutic benefit of injected microrods in the setting of chronic ischemic
cardiomyopathy as suggested by preliminary in vivo results. Therapeutic effect after microrod injection will be
measured by serial echocardiograms to assess ejection fraction and cardiac anatomy in relation to the infarct
scar and angiogenesis. By decreasing fibrotic scarring, inducing angiogenesis and promoting myocardial
regeneration, injectable microrods will contribute to improving outcomes after MI. Understanding these
mechanisms will lead to the design and optimization of complementary therapies and drug delivery
possibilities, which will further the NHLBI's mission of treating hear...

## Key facts

- **NIH application ID:** 9842927
- **Project number:** 5R01HL137209-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Tejal A. Desai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,590
- **Award type:** 5
- **Project period:** 2017-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842927

## Citation

> US National Institutes of Health, RePORTER application 9842927, Microstructural Cues for the Treatment of Heart Failure (5R01HL137209-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842927. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*