Piezo1: Sensing Forces to Steer Brain Vascular Dynamics

Dr. Omar Harraz is a professor of Pharmacology at the University of Vermont.

Increases in blood flow (hyperemia) in response to neural activity is essential for brain health. A hyperemic response delivers oxygen and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia—neuronal activity-to-vascular response—the mechanical consequences of hyperemia have gone largely unexplored. Piezo1 is an endothelial mechanosensor that senses hyperemia-associated forces. In this seminar, I will present our research using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, and how we evaluated its role in blood flow control. We found evidence of a built-in brake system that sculpts hyperemia, and specifically show that Piezo1 activation triggers a mechano-feedback system that promotes blood flow recovery to baseline. Further, genetic Piezo1 modification led to deficits in complementary memory tasks. I will also present recent data showing how this mechano-feedback control system breaks down in disease.

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Hosted by Dr. Amy Lee

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