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Thesis Format

Monograph

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Dwayne Jackson

Abstract

Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and after Grammostola Mechanotoxin 4 (GsMTx4) incubation to blocking Piezo1 channels, to quantify the homeostatic response of arterioles before and after Piezo1 antagonism. We are able to report Piezo1 as indispensable component in vascular smooth muscle cells (VSMC) and Endothelial cells (EC) to sense and change vessel diameter based on intravascular pressure and shear stress, correspondingly. Also, we report for the first time a heterogeneous response in males and females after Piezo1 antagonism in representative resistance arterioles from the skeletal muscle and cerebral circulation.

Summary for Lay Audience

Piezo proteins are found in cell’s membranes and specialize in detecting mechanical forces (e.g. friction and pressure) and translating this information into signals that promote proper cellular function. To date, the study of Piezo proteins has helped understand diverse cellular mechanisms and their importance in the context of heart and blood vessel diseases. Nevertheless, Piezo1’s role in the regulation of the smallest vessels in the body and how Piezo 1 function may vary between males and females, has remained unstudied. We focused on blood vessels from the skeletal muscle and cerebral circulations, due to their natural differences in regulating blood flow. The main objective of our project was to understand Piezo 1’s role in their unique regulation properties and if the negative effects of Piezo 1 dysfunction impact differently on males and females. By approaching our project contemplating sex and anatomical differences, we have opened up the field to using Piezo1 as a potential target for therapies to provide more effective treatments for cardiovascular diseases in males and females.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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