# Critical Role of Endothelial DRP1 in regulating metabolic, microvascular, and cardiac function

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $53,314

## Abstract

Project Summary/Abstract:
Microvascular endothelial-dependent vasodilation in response to flow is achieved by the release of nitric oxide
(NO) in healthy individuals but is mediated by hydrogen peroxide (H2O2) in individuals with coronary artery
disease (CAD). Mitochondria are potent producers of reactive oxygen species (ROS), including H2O2, under
physiological conditions, but overproduce ROS in cardiometabolic pathologies. Mitochondrial fission and
fusion are known regulators of ATP and ROS production. Mitochondrial fission is primarily mediated by and
dependent on the GTPase, dynamin-related protein 1 (DRP1). Hyper-fission, due to increased levels of or
overactivation of DRP1, has been implicated in promoting cellular dysfunction in various cardiometabolic
diseases. Our preliminary data indicate that blocking DRP1 may have vascular benefits for individuals with
CAD and that the overexpression of endothelial DRP1 contributes to vascular dysfunction in both humans and
rats. We therefore hypothesize that DRP1 and mitochondrial fission may be important regulators of endothelial
vascular function. The overall goal of this proposal is to assess the role of endothelial DRP1 in vivo using a novel
rodent model that drives the overexpression of a DRP1-GFP transgene specifically in the vascular
endothelium. Aim 1 will investigate whether DRP1 mediates mitochondrial fragmentation and metabolic
changes in the endothelium in both isolated endothelial cells and intact blood vessels. Aim 2 will determine if
upregulated endothelial cell DRP1 leads to functional damage in the microvasculature and the heart.

## Key facts

- **NIH application ID:** 10995690
- **Project number:** 1F31HL176057-01
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Cristhian A Gutierrez Huerta
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,314
- **Award type:** 1
- **Project period:** 2024-09-30 → 2027-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995690

## Citation

> US National Institutes of Health, RePORTER application 10995690, Critical Role of Endothelial DRP1 in regulating metabolic, microvascular, and cardiac function (1F31HL176057-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10995690. Licensed CC0.

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