# Metabolism and cell cycle as mediators of fluid shear stress effects on vascular endothelium in health and disease

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $798,343

## Abstract

Project Summary
This project is based on the critical role of fluid shear stress from blood flow acting on the
vascular endothelium in determining susceptibility to atherosclerosis. Physiological levels of
laminar shear stress are actively anti-inflammatory and promote disease resistance whereas
disturbed fluid shear stress amplifies inflammatory and metabolic risk factors to promote
disease. Preliminary and published data implicate endothelial cell metabolism as critical in the
differential effects of laminar vs disturbed flow, including a mitochondrial pathway activated
through Piezo1 mechanosensitive channels, yet these effects, indeed, the entire area, is poorly
understood. Our preliminary data also implicate cell cycle as a critical part of these regulatory
effects, with a late G1 arrested state in which the cyclin-dependent kinase Cdk2 is active as a
key inhibitor of atherogenic pathways. We therefore propose: 1) A thorough unbiased analysis
of effects of laminar vs disturbed shear stress on endothelial metabolism, with in vivo analysis of
Piezo1 loss and gain of function mutants, and extensive analysis to link metabolic effects to
disease pathways; 2) In vitro mechanistic and in vivo pre-clinical analysis of the role of Cdk2 in
endothelial inflammatory activation and disease, including links to metabolic pathways.

## Key facts

- **NIH application ID:** 10945294
- **Project number:** 1R01HL175052-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Martin A Schwartz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $798,343
- **Award type:** 1
- **Project period:** 2024-08-13 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945294

## Citation

> US National Institutes of Health, RePORTER application 10945294, Metabolism and cell cycle as mediators of fluid shear stress effects on vascular endothelium in health and disease (1R01HL175052-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10945294. Licensed CC0.

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