# Cardiac microtubules as regulators of diastolic function.

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2024 · $540,365

## Abstract

Abstract
Diastolic heart disease (DHD) is the leading cause of death and disability worldwide. With no FDA approved
therapies to improve diastolic function, the NIH has placed special emphasis on collaborative initiatives bridging
basic science and clinical data to understanding the molecular mechanism of DHD. The hallmarks of diastolic
heart disease are a stiffening left ventricle and an inability for the heart muscle to relax, both of which occur in
DHD by mechanisms that are poorly understood. Building on recent work that the cardiac microtubule network
(MTN) can both stiffens and impairs the relaxation of failing cardiomyocytes, in Aim 1 we determine the relative
contribution of the MTN to myocardial stiffness in intact preparations of HTN and DHD ventricular myocardium.
We isolate the myocyte and fibrotic contribution to stiffening and use complimentary reductionist approaches to
isolate the relative contributions of actomyosin activity, passive titin stiffness, and the MTN to myocyte
mechanics. In Aim 2 we extend these findings into a clinically analogous ex-vivo working myocardial slice
preparation to dissect the MTN impediment to the phases of diastole in HTN and DHD. The working preparation
allows us to contextualize the findings in Aim 1 with the emergent properties arising from cyclically contracting
loaded myocardium. Thus, by carefully designing a series of complementary assays we will resolve the
molecular contributions to cardiac stiffening and impaired relaxation in DHD, and in doing so determine the
potential for MTN-targeting therapies in DHD.

## Key facts

- **NIH application ID:** 10779971
- **Project number:** 1R01HL171614-01
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Matthew Caporizzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $540,365
- **Award type:** 1
- **Project period:** 2023-12-12 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779971

## Citation

> US National Institutes of Health, RePORTER application 10779971, Cardiac microtubules as regulators of diastolic function. (1R01HL171614-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10779971. Licensed CC0.

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