# Targeting Mas Receptor for Diabetic Vascular Disease in Older Adults

> **NIH NIH R01** · NORTH DAKOTA STATE UNIVERSITY · 2021 · $253,750

## Abstract

Targeting Mas Receptor for Diabetic Vascular Disease in Older Adults
Abstract
Prevalence of diabetes is high among older adults and is expected to rise, and diabetes increases risk for
cardiovascular disease. Accumulated evidence suggests that bone marrow-derived progenitor cells maintain
vascular health and promote rapid repair following vascular injury. This innate vascular protection is
diminished with aging and diabetes due to impaired mobilization of EPCs from bone marrow into circulation
and decreased ability to repair damaged blood vessels. Therefore approaches that preserve EPC mobilization
and function will prevent the development of vascular disease in older adults with diabetes. We hypothesize
that the Mas receptor, the functional mediator of the vasoprotective axis of renin angiotensin system, confers
mobilization and reparative functions in EPCs and that early intervention with MasR activation would
preserve innate vasoprotection and prevents the development of vascular disease with aging and diabetes.
This hypothesis is based on our novel findings that showed angiotensin converting enzyme-2 that generates
heptapeptide angiotensin (Ang)-(1-7), the endogenous activator of MasR, is down-regulated with aging and
diabetes. Importantly, genetic deficiency of MasR (MasR-KO) precipitates EPC moblilopathy and
vasoreparative dysfunction following ischemic vascular injury, similar to aging and diabetes. Three aims are
proposed to test the hypothesis. Aim-1 will define the role of MasR in the mobilization and vasoreparative
functions of EPCs by using radiation chimeras of MasR-KO mice. Aim-2 will test the beneficial effects of long-
term activation of MasR on the development of vasoreparative dysfunction with aging and diabetes. This will
be accomplished by overexpressing Ang-(1-7) by adenoviral or nonviral approaches. We will test if the
overexpression of Ang-(1-7) will reverse the vasoreparative dysfunction in CD34+EPCs derived from older
adults with diabetes. Therefore Aim-2 will provide the proof-of-concept for the translational potential of the
study. Aim 3 will demonstrate the involvement of novel pathways that mediate the reversal of mobilization
and vasoreparative dysfunctions in diabetic EPCs by MasR activation, Slit/Robo/ROCK pathway and
TERT/mitoROS/NO pathway, respectively. Overall, this study will provide a novel mechanism-based
pharmacological approach for reversal as well as prevention of diabetic vascular disease in older adults with
diabetes.

## Key facts

- **NIH application ID:** 10180827
- **Project number:** 5R01AG056881-05
- **Recipient organization:** NORTH DAKOTA STATE UNIVERSITY
- **Principal Investigator:** Yagna Jarajapu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $253,750
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180827

## Citation

> US National Institutes of Health, RePORTER application 10180827, Targeting Mas Receptor for Diabetic Vascular Disease in Older Adults (5R01AG056881-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180827. Licensed CC0.

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