Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release
Open accessAbstract
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS. We also demonstrated that PIEZO1-dependent ATP release is mediated in part by pannexin channels. The PIEZO1 activator Yoda1 mimicked the effect of fluid shear stress on endothelial cells and induced vasorelaxation in a PIEZO1-dependent manner. Furthermore, mice with induced endothelium-specific PIEZO1 deficiency lost the ability to induce NO formation and vasodilation in response to flow and consequently developed hypertension. Together, our data demonstrate that PIEZO1 is required for the regulation of NO formation, vascular tone, and blood pressure.
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Piezo1 channels are vital for numerous physiological processes, including cell migration and differentiation, cardiovascular development, blood pressure regulation, and immune modulation.
“In addition to mechanosensation, Piezo1 channels are vital for numerous physiological processes, including cell migration and differentiation,33 cardiovascular development,34 blood pressure regulation,35 and immune modulation.36”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [33]
Most endothelial cells express Piezo1 in the mRNA and protein forms.
“Numerous studies have indicated that most endothelial cells express Piezo1 in the mRNA and protein forms.33,34,82,83,84,85,86”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [33]
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- Authors
- Wang, S., Chennupati, R., Kaur, H., Iring, A., Wettschureck, N., & Offermanns, S.
- Affiliations
- Max Planck Society (DE)
- Goethe University Frankfurt (DE)
- Venue
- Journal of Clinical Investigation
- Published
- 2016-10-31
- Volume
- 126
- Issue
- 12
- Pages
- 4527-4536
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5127677
- OpenAlex
- W2542750476
- Cited by
- 616
- References
- 6
- Citations by year
- 2026: 62 · 2025: 80 · 2024: 80 · 2023: 79 · 2022: 84 · 2021: 76 · 2020: 50 · 2019: 50 · 2018: 35 · 2017: 18 · 2016: 1
- FWCI
- 31.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- Piezo1, fluid shear stress, pannexin channels, P2Y2 receptor, nitric oxide, endothelial nitric oxide synthase, Akt phosphorylation, vasodilation, blood pressure regulation, hypertension, Yoda1, vascular tone
- MeSH terms
- Animals, Blood Pressure, Calcium, Cattle, Humans, Ion Channels, Phosphorylation, Vasodilation, Calcium Signaling, Proto-Oncogene Proteins c-akt, Mice, Nitric Oxide Synthase Type III, Receptors, Purinergic P2Y, Human Umbilical Vein Endothelial Cells
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