# Notch1/miR-322 Axis in Stem Cell Mediated Vascular Repair

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $621,413

## Abstract

PROJECT SUMMARY
Cardiac mesenchymal stem cells (C-MSC) are a unique pool of stem cells residing in the heart
that play an important role in vascular homeostasis and physiological vascular cell turnover.
Transplanting C-MSC into the heart has shown promise for vessel repair and angiogenesis,
but poor survival of transplanted cells poses a major technical challenge. We reported that
hypoxic preconditioning (HP) improves donor stem cell survival and angiogenesis in a HIF-1α-
dependent manner. Mechanistically, C-MSC responses to HP correlate with the level of
activation of Notch signaling, a cell-cell contact and pathway in stem cells that also mediates
vascular smooth muscle cell (VSMC) differentiation of C-MSC. Moreover, we have identified a
Notch-regulated microRNA, miR-322, the rodent homolog of human miR-424, which was
reported to promote angiogenesis by blocking degradation of HIF-1α isoforms in human
endothelial cells during hypoxia, suggesting a novel mechanism of crosstalk between Notch-
regulated miR-322 and HIF-1α. We propose to investigate how Notch-1 and the newly
identified Notch-1 target miR-322 sustain and potentiate the beneficial effects of HP on the
vascular cell survival and angiogenic activity of stem cells. We will also determine whether
harnessing these regulatory mechanisms in stem cells can enhance vessel protection and
repair in a mouse model of myocardial infarction (MI). There are three aims: Aim 1: Test the
hypothesis that Notch signaling regulates the beneficial effects of HP in stem cell-mediated
vascular repair. Aim 2: Test the hypothesis that miR-322 mediates crosstalk between Notch1
and HIF-1α signaling in stem cells to enhance their activity. Aim 3: Test the therapeutic
potential of targeting the Notch1/miR-322 axis to enhance stem cell-mediated vascular repair
and angiogenesis in a mouse model of MI. Successful completion of the proposed studies will
elucidate novel mechanisms associated with C-MSC mediated vascular repair and
angiogenesis and enhance the efficacy of C-MSC therapy.

## Key facts

- **NIH application ID:** 9923003
- **Project number:** 5R01HL134354-04
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Muhammad Ashraf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $621,413
- **Award type:** 5
- **Project period:** 2016-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923003

## Citation

> US National Institutes of Health, RePORTER application 9923003, Notch1/miR-322 Axis in Stem Cell Mediated Vascular Repair (5R01HL134354-04). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9923003. Licensed CC0.

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