Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow
Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O<sub>2</sub> 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. Using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, we evaluated its role in blood flow control and whether it impacts cognition. We provide 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. Collectively, our findings establish a role for endothelial Piezo1 in cerebral blood flow regulation and a role in its behavioral sequelae.
Authors
- Markus Schwaninger (ORCID: https://orcid.org/0000-0002-4510-9718)
- Thomas A. Longden (ORCID: https://orcid.org/0000-0002-7950-7677)
- Masayo Koide (ORCID: https://orcid.org/0000-0002-1381-7074)
- Dmitry D. Postnov (ORCID: https://orcid.org/0000-0002-9708-8453)
- Xin Rui Lim (ORCID: https://orcid.org/0000-0002-4166-0377)
- Dorothea Ziemens
- Kathryn Laprade
- M. Ippolito (ORCID: https://orcid.org/0009-0007-0135-0415)
- Ashwini Hariharan (ORCID: https://orcid.org/0000-0003-1734-4443)
- Jan Wenzel (ORCID: https://orcid.org/0000-0001-6313-2439)
- Nick Weir (ORCID: https://orcid.org/0000-0001-5133-7832)
- Amanda J. Senatore (ORCID: https://orcid.org/0000-0002-8743-1537)
- Osama F. Harraz (ORCID: https://orcid.org/0000-0003-2061-1100)
- James M. Stafford (ORCID: https://orcid.org/0000-0002-1435-6898)
- Curtis Plante
- Mohammad Mahmoud Abd-Alhaseeb (ORCID: https://orcid.org/0000-0001-5388-5250)
Institutions
- University of Vermont (US)
- University of Maryland, Baltimore (US)
- Aarhus University (DK)
- German Centre for Cardiovascular Research (DE)
- Vermont Department of Health (US)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-07
- DOI
- https://doi.org/10.1038/s41467-024-52969-0
- Citations
- 46
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 15.02
Funders
- Silicon Valley Community Foundation
- American Heart Association
- Deutsche Forschungsgemeinschaft
- Lundbeckfonden
- Universität zu Lübeck
- H. Lundbeck A/S
- Totman Medical Research Trust, University of Vermont
- Larner College of Medicine, University of Vermont
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- Cardiovascular Research Institute of Vermont, Larner College of Medicine, University of Vermont