# Epigenetic regulation of vascular endothelial genes and laminar flow atheroprotection

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2022 · $385,000

## Abstract

Atherosclerosis is the major cause of death and disability in the United States and
throughout the world. The lesions of atherosclerosis have a non-uniform distribution in
the human vasculature. Straight regions of arteries are exposed to steady laminar blood
flow (L-flow) and are protected from atherosclerosis, whereas regions of bifurcations and
curvatures are characterized by disturbed blood flow (D-flow) that are predisposed to
atherosclerosis. It is unrealistic to alter the architecture of the human vascular tree such
as elimination of the arterial curvature or bifurcation; however, if we completely
understand the signaling pathways conferring L-flow atheroprotection, we will be able to
produce the atheroprotective action in D-flow areas of arteries by pharmacological or
molecular means to prevent atherogenesis. Thus, our central goal is to identify the key
signaling molecules in the anti-atherogenic programs of L-flow and to explore whether
targeting these molecules could lead to atheroprotection in the D-flow regions of arteries.
In our recent preliminary studies we have uncovered a unique epigenetic pathway that
contributes to differential regulation of endothelial gene transcription programs in
response to the atheroprotective laminar flow versus the atheroprone disturbed flow. In
this proposal, we will explore the H3K27me3-dependent epigenetic mechanisms
underlying L-flow versus D-flow effects on endothelial gene expression and
atherosclerosis using the combinations of cell culture systems and animal models.
Results from our proposed studies will reveal important and innovative molecular
mechanisms underlying the hemodynamic forces-dependent atherogenesis, which may
identify new therapeutic strategies for the treatment of atherosclerotic vascular diseases.

## Key facts

- **NIH application ID:** 10430272
- **Project number:** 5R01HL141171-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** ZHENG-GEN JIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2019-07-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430272

## Citation

> US National Institutes of Health, RePORTER application 10430272, Epigenetic regulation of vascular endothelial genes and laminar flow atheroprotection (5R01HL141171-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10430272. Licensed CC0.

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