Journal Article Preprint Epublish 1 citation
PubMed: 38915529 DOI: 10.1101/2024.06.11.598539
Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries.
bioRxiv
Authors: Javier Abello, Ying Yin, Yonghui Zhao, Josh Maurer, Jihui Lee, Cherokee Bodell, Abigail J Clevenger, Zarek Burton, Megan E Goeckel, Michelle Lin, Stephanie Grainger, Carmen M Halabi, Shreya A Raghavan, Rajan Sah, Amber N Stratman
Affiliations
- Department of Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
- Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, USA.
- Center for Cardiovascular Research, Washington University, St Louis, MO, USA.
Abstract
Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased levels and decreased vSMC association with arteries. We supported the small molecule data with genetic suppression of and in zebrafish, resulting in loss of vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine mechanism, we used modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature.
MeSH
Cells, Muscle Cells, Cell Differentiation, Muscles, Muscle, Smooth, Aorta, Arteries, Endothelial Cells, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Veins, Small Molecules