# Autophagy and diabetic vascular diseases

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2020 · $609,904

## Abstract

Project Summary
Overwhelming evidence suggest that mitochondria plays a causative role in diabetic endothelial
dysfunction. How mitochondria become dysfunctional remains enigmatic. Our exciting preliminary data
indicate that diabetes instigates aberrant mitochondrial fission by suppressing autophagy-dependent
degradation of the dynamin-related protein 1 (DRP1), a molecule essential for mitochondrial fission.
The central hypothesis of this application that selective impairment autophagy-mediated DRP1
degradation in diabetes instigates vascular endothelial dysfunction and accelerates
atherosclerosis. This hypothesis will be tested using gain-/loss-of-function strategies in both animal
models and cultured cells. Aim 1 is to test the hypothesis that defective vascular autophagy increases
mitochondrial fission in the development of endothelial dysfunction and atherosclerosis by
characterizing the spatial and temporal dynamics of vascular autophagy, mitochondrial fission, and
endothelial dysfunction in Akita mice (type 1 diabetes) and ob/ob mice (type 2 diabetes), determining
whether inhibition of autophagy aggravates mitochondrial fission, endothelial dysfunction, and
atherosclerosis in diabetic LDLr-/-/beclin1 heterozygous (beclin1+/-, with reduced autophagy) mice and
their littermates, and examining whether enhanced endothelial autophagy lessens oxidative stress and
improves endothelial function in diabetic Atg7 endothelium-specific transgenic mice (with enhanced
autophagy). Aim 2 is to delineate the mechanisms by which diabetes-inhibited autophagy increases
mitochondrial fission. This aim will test the hypothesis that diabetes induces mitochondrial fission by
inhibiting autophagic degradation of DRP1. Proposed studies are significant as the completion of this
proposal will provide the rationales for developing new therapeutics to prevent/treat cardiovascular
complications in diabetes.

## Key facts

- **NIH application ID:** 9926299
- **Project number:** 5R01HL079584-18
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** MING-HUI ZOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $609,904
- **Award type:** 5
- **Project period:** 2004-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926299

## Citation

> US National Institutes of Health, RePORTER application 9926299, Autophagy and diabetic vascular diseases (5R01HL079584-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9926299. Licensed CC0.

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