# Flow-dependent endothelial cell signaling

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $268,500

## Abstract

Project Summary
Cardiovascular disease continues to be the major cause of morbidity and mortality in the United
States, and is an emerging epidemic world-wide. In particular atherosclerosis is a life-threatening
disease strongly associated with risk factors such as hypercholesterolemia, hypertension and
diabetes. Importantly, in the face of these potent systemic drivers of cardiovascular risk, certain
regions of the arterial vasculature nonetheless remain relatively resistant to the development of
atherosclerotic lesions. Several lines of evidence suggest that hemodynamically distinct
environments in these arterial geometries exert a protective influence on the vascular
endothelium, thus inhibiting early lesion development. However, despite recent progress in our
understanding of the transcriptional activators responsible for this “vasoprotection”, this progress
has not yet been translated into therapeutic strategies for cardiovascular disease due to the lack
of mechanistic understanding of the proximal signaling pathways activated by vasoprotective
flow. In this project, previously unrecognized actions of doxorubicin in vascular endothelial cells,
recently uncovered in our laboratory, will provide the basis for establishing a novel conceptual
and experimental framework seeking to identify novel mechano-activated signaling pathways in
the vascular endothelium. To this end, we will perform a loss-of-function screen in human
endothelial cells to gain insights into the mechanism of action of doxorubicin-mediated loss of
flow-dependent endothelial vasoprotection. Ultimately, the identification of the molecular
target(s) of doxorubicin in endothelial cells should contribute to our understanding of how these
cells sense, integrate and respond to vasoprotective flow, and could help in the development on
new therapeutic interventions against endothelial cell dysfunction.

## Key facts

- **NIH application ID:** 9969959
- **Project number:** 1R21HL152367-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Guillermo Garcia-Cardena
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $268,500
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969959

## Citation

> US National Institutes of Health, RePORTER application 9969959, Flow-dependent endothelial cell signaling (1R21HL152367-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969959. Licensed CC0.

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