Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance
Open accessAbstract
Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca 2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control.
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Piezo1 channels are present in LSECs in both mice and humans, affecting vascular stability, including endothelial cell vasodilation, tension, and blood flow regulation.
“Recent studies have identified Piezo1 channels in LSECs in both mice and humans,34,43,45,83 which affect vascular stability, including endothelial cell vasodilation, tension, and blood flow regulation.44”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [34]
Citation 44 is attached to the vascular-effects clause, not the claim that Piezo1 is present in mouse and human LSECs. The Introduction and Results describe endothelial Piezo1 affecting vascular tone, blood pressure, and the redistribution of blood flow during exercise, particularly through flow-induced vasoconstriction in mouse mesenteric arteries. They do not establish the broader claim about vascular stability or a general Piezo1-mediated vasodilation effect. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMost 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 [34]
In Results (‘Constitutive and flow-induced Piezo1 in mesenteric artery’; page unavailable), the paper reports native Piezo1 channel activity in cultured endothelial cells and says that activity is common in mesenteric artery endothelial cells. This supports Piezo1 protein being present in the endothelial cells studied, but the passages do not establish mRNA expression or that most endothelial cells generally express Piezo1. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPiezo1 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 [34]
Piezo1 expression in liver cells follows a multimodal distribution pattern, with varying degrees of expression in the biliary system, liver sinusoidal microvasculature, portal vein narrow areas, and liver parenchyma.
“Several studies have demonstrated that Piezo1 expression in cells follows a multimodal distribution pattern, with varying degrees of expression in the biliary system,39 liver sinusoidal microvasculature, portal vein narrow areas,34,43 and liver parenchyma.”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [34]
The Methods section describes isolating mouse liver sinusoidal endothelial cells, but does not report Piezo1 expression in them. The Results passages concern mesenteric artery endothelium and liver histology, not a distribution of Piezo1 across the biliary system, portal vein, and liver parenchyma. Searches for those liver structures and a multimodal expression pattern found no supporting passage; page numbers are unavailable in our copy. (LLM, conf=0.72)
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PIEZO Ion Channels in Cardiovascular Functions and Diseases
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Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries
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Piezo1 mediates endothelial atherogenic inflammatory responses via regulation of YAP/TAZ activation
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Mechanosensing Piezo channels in tissue homeostasis including their role in lungs
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Mechanosensitive Piezo1 channel in physiology and pathophysiology of the central nervous system
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Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow
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Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts
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Physiology and Pathophysiology of Mechanically Activated PIEZO Channels
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Endothelial Ion Channels and Cell-Cell Communication in the Microcirculation
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Piezo1 Response to Shear Stress Is Controlled by the Components of the Extracellular Matrix
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The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function
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Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity
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Self-citationImproved PIEZO1 agonism through 4‐benzoic acid modification of Yoda1
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Self-citationPiezo1 channels are mechanosensors in human fetoplacental endothelial cells
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Self-citationFluid shear stress facilitates prostate cancer metastasis through Piezo1-Src-YAP axis
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Piezo channels in the urinary system
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Self-citationVascular Smooth Muscle Cells Mechanosensitive Regulators and Vascular Remodeling
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The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals
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Piezo1 channel activation mimics high glucose as a stimulator of insulin release
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Self-citationModeling of full-length Piezo1 suggests importance of the proximal N-terminus for dome structure
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Self-citationEarly events in endothelial flow sensing
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Tubeimoside I Antagonizes Yoda1-Evoked Piezo1 Channel Activation
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COMP (Cartilage Oligomeric Matrix Protein), a Novel PIEZO1 Regulator That Controls Blood Pressure
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Self-citation
- Authors
- Rode, B., Shi, J., Endesh, N., Drinkhill, M. J., Webster, P. J., Lotteau, S. J., Bailey, M. A., Yuldasheva, N. Y., Ludlow, M. J., Cubbon, R. M., Li, J., Futers, T. S., Morley, L., Gaunt, H. J., Marszalek, K., Viswambharan, H., Cuthbertson, K., Baxter, P. D., Foster, R., Sukumar, P., Weightman, A., Calaghan, S. C., Wheatcroft, S. B., Kearney, M. T., & Beech, D. J.
- Affiliations
- University of Leeds (GB)
- University of Manchester (GB)
- Corresponding author
- Beech, David J.
- ORCID
- Shi, Jian
- Endesh, Naima
- Drinkhill, Mark J.
- Lotteau, Sabine J.
- Bailey, Marc A.
- Yuldasheva, Nadira Y.
- Ludlow, Melanie J.
- Cubbon, Richard M.
- Li, Jing
- Futers, T. Simon
- Morley, Lara
- Marszalek, Katarzyna
- Viswambharan, Hema
- Cuthbertson, Kevin
- Baxter, Paul D.
- Foster, Richard
- Sukumar, Piruthivi
- Weightman, Andrew
- Calaghan, Sarah C.
- Wheatcroft, Stephen B.
- Kearney, Mark T.
- Beech, David J.
- Venue
- Nature Communications
- Published
- 2017-08-24
- Volume
- 8
- Issue
- 1
- Pages
- 350-350
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5571199
- OpenAlex
- W2747918806
- Cited by
- 305
- References
- 32
- Citations by year
- 2026: 37 · 2025: 31 · 2024: 44 · 2023: 32 · 2022: 49 · 2021: 40 · 2020: 18 · 2019: 31 · 2018: 20 · 2017: 3
- FWCI
- 12.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (110044/Z/15/Z)
- National Institute for Health and Care Research (ACF-2014-02-003)
- British Heart Foundation (RG/15/7/31521, PG/12/88/29951, FS/12/80/29821, FS/14/22/30734, FS/17/2/32559)
- Medical Research Council (MR/L019051/1, MR/P002099/1)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- Piezo1, mechanical force sensing, endothelium-dependent relaxation, mesenteric resistance arteries, blood pressure, vasoconstriction, voltage-gated calcium channels, vascular smooth muscle, physical performance, weight loss, cardiovascular homeostasis
- MeSH terms
- Animals, Blood Pressure, Cells, Cultured, Homeostasis, Humans, Ion Channels, Male, Physical Conditioning, Animal, Vasoconstriction, Patch-Clamp Techniques, Calcium Signaling, Myocytes, Smooth Muscle, Endothelial Cells, Mice, HEK293 Cells
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