# Brain Capillary Mechanosensation by Piezo1 Channels in Health and Disease

> **NIH NIH P20** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $257,095

## Abstract

Cerebral blood flow is exquisitely controlled to satisfy neuronal metabolic demands. An essential feature of this control 
is the on-demand increase in local blood flow triggered by neural activity; a process termed functional hyperemia (FH) 
that is coordinated by multiple neurovascular coupling mechanisms. Importantly, the increases in shear stress in 
response to enhanced blood flow constitute mechanical forces with the potential to impact vascular behavior. A 
growing body of evidence indicates that hypertension attenuates FH. Notably, uncontrolled elevation of blood 
pressure is associated with dramatic alterations in the hemodynamic forces imposed on the vasculature. However, the 
extent to which mechanosensitive properties of the cerebral circulation are impacted by hypertension has not been 
explored. Piezo1, a Ca2+/Na+-permeable, mechanosensitive channel expressed in vascular endothelial cells, is the 
major mechanosensor in brain capillaries. Intriguingly, a gain-of-function mutation in the PIEZO1 gene has been 
reported in African Americans populations, which show the highest prevalence of hypertension in the world (>40%). 
Based on the unique properties of Piezo1 channels and the essential role of endothelial Ca2+ signaling in FH, I will 
evaluate the following hypotheses: (1) brain capillary Piezo1 channel activity is altered during hypertension; and (2) 
this change in Piezo1 function is implicated in the deficits in FH that occur during hypertension. These hypotheses will 
be tested by directly measuring Piezo1 channel activity and by measuring cerebral blood flow in the context of normal 
and high blood pressure. We will use technical innovations introduced by our laboratory that include cutting-edge 
genetically engineered mouse models with increased or decreased Piezo1 activity and mice with endothelial-specific 
genetically encoded Ca2+ indicators. By viewing hyperemic 'responses' through a new lens as mechanical 'stimuli', the 
proposed studies envision normal and perturbed (i.e., hypertension) cerebral blood flow from a completely fresh 
perspective. This project has the potential to profoundly alter our understanding of cerebral blood flow dysregulation 
during hypertension and may reveal sorely needed new paths to treatment.

## Key facts

- **NIH application ID:** 10447833
- **Project number:** 5P20GM135007-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Osama F Harraz
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $257,095
- **Award type:** 5
- **Project period:** 2020-08-06 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447833

## Citation

> US National Institutes of Health, RePORTER application 10447833, Brain Capillary Mechanosensation by Piezo1 Channels in Health and Disease (5P20GM135007-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447833. Licensed CC0.

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