# MyomiR-499, Exosomes and Endothelial and Endothelial Progenitor Cells dysfunction in Diabetes

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $616,776

## Abstract

PROJECT SUMMARY/ABSTRACT
Diabetes mellitus is a common chronic metabolic disease imposing great social and economic burden,
and is considered as one of the major health-threats in USA and worldwide. The morbidity of critical limb
ischemia (CLI) in diabetic patients is extremely high (up to 76% in some studies). Therefore,
understanding the mechanisms of CLI pathogenesis in diabetes is critical for developing novel
therapeutic strategies. We and others have reported that enhancing endothelial cell (EC) and endothelial
progenitor cell function improves ischemic tissue repair. Recently, there is growing evidence indicating
that diabetes severely impairs angiogenic property of EC/EPC that may directly limit CLI repair. The
overall goal of this proposal is to elucidate the role of muscle-specific miR-499 in diabetes-impaired
EC/EPC function. The premise of our proposed studies is based on our preliminary studies showing that
expression of miR-499, a muscle-specific miR, was enhanced in EC/EPCs from db/db mice. Our central
hypothesis is that diabetes e nhanced miR-499 impairs EC/EPCs function and ischemic limb repair
via skeletal muscle-derived exosomal delivery of miR-499 to EC/EPCs. We propose to conduct
complementary experiments organized under the following 3 aims: 1. Determine the role of miR-499 in
diabetes-induced EC and EPC dysfunction; 2. Demonstrate the role of muscle-derived
exosomes in miR-499-induced EC dysfunction in diabetes; 3. Elucidate the molecular signaling
downstream of miR-499 involved in diabetes-impaired angiogenic property of EC. Our findings will
provide fundamental insights into development of novel strategies for therapeutics of CLI in diabetic
patients.
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## Key facts

- **NIH application ID:** 10878381
- **Project number:** 1R01HL169405-01A1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Raj Kishore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,776
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878381

## Citation

> US National Institutes of Health, RePORTER application 10878381, MyomiR-499, Exosomes and Endothelial and Endothelial Progenitor Cells dysfunction in Diabetes (1R01HL169405-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10878381. Licensed CC0.

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