# SIRT6 and vascular endothelial homeostasis

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $385,000

## Abstract

The major goal of the project is to elucidate the molecular mechanism underlying
diabetes-associated vascular endothelial dysfunction. Diabetes mellitus, one of the
major leading chronic morbidities worldwide, is continually increasing with a high
prevalence in the United States and throughout the world. Cardiovascular complications
are mainly responsible for the high morbidity and mortality in people with diabetes.
Vascular endothelial dysfunction in diabetes mellitus critically contributes to the
pathogenesis of atherosclerotic disease and its cardiovascular complications. However,
the exact molecular mechanisms of endothelial dysfunction in diabetes remain largely
unknown. SIRT6, a new member of the sirtuin family of proteins, has recently recognized
as a master regulator of stress resistance, gene transcription, genome stability and
metabolic homeostasis. SIRT6 has distinct cellular localization and function from other
sirtuin family members such as well-studied SIRT1. Recent studies indicate that SIRT6
deficiency is associated with metabolic disease, and SIRT6 has been proposed as a
potential therapeutic candidate fighting the metabolic syndrome epidemic. In parallel,
emerging evidence from our group suggests that SIRT6 plays a crucial role in regulation
of endothelial homeostasis and endothelial SIRT6 deficiency is associated with diabetes.
As such we propose that an alternation of SIRT6 expression in diabetes could result in
endothelial dysfunction and thus a predisposition to atherosclerosis, and resorting SIRT6
function could improve endothelial homeostasis and protects against atherosclerosis in
diabetes. We will use the combination of in vitro and in vivo experiments to test this
novel hypothesis. Results from our proposed studies, if as anticipated, would help to
understand the molecular basis of endothelial dysfunction, and facilitate the
development of new therapeutic approaches, such as enhancing SIRT6 expression and
activity, to limit diabetes-accelerated atherosclerotic cardiovascular diseases.

## Key facts

- **NIH application ID:** 9900038
- **Project number:** 5R01HL130167-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** ZHENG-GEN JIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900038

## Citation

> US National Institutes of Health, RePORTER application 9900038, SIRT6 and vascular endothelial homeostasis (5R01HL130167-04). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9900038. Licensed CC0.

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