ArticleThe Journal of clinical investigation2015
P2Y₂ and Gq/G₁₁ control blood pressure by mediating endothelial mechanotransduction.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Knowledge domain and evolutionary trends of P2Y receptors in cardiovascular diseases: a bibliometric and altmetric analysis.Frontiers in pharmacology · 2025Pooled it
- Brain endothelial GαEBioMedicine · 2026Article
- Vascular mechanical forces and vascular diseases.Journal of advanced research · 2026Review
- Endothelial soluble APP/APLP2 promote heart repair through KIT-mediated angiogenesis.Science advances · 2026Article
- The Piezo1-Ca2+-PI3k/Akt signaling axis as a context-dependent mechanotransduction node during skin wound healing.iScience · 2026Review
- Exploring the application of shear stress in erectile dysfunction.Asian journal of andrology · 2026Review
- Blood-borne sphingosine 1-phosphate maintains vascular resistance, blood pressure, and cardiac function in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Bibliometric Analysis of P2X7R in Cardiovascular Diseases from 2005 to 2024.Current cardiology reviews · 2026Review
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- Swimming motions evoke Piezo1-dependent CaCurrent biology : CB · 2025Article
- Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery.Purinergic signalling · 2025Article
- Mechanosensing of Shear Stress and Uterine Spiral Artery Remodeling by Invasive Trophoblasts in Early Pregnancy.International journal of molecular sciences · 2025Review
- Effects of SGLT2 inhibitors on ion channels in heart failure: focus on the endothelium.Basic research in cardiology · 2025Review
- Photoacoustic microscopy for studying mechano-transduction response in resistance vessels.Photoacoustics · 2025Article
- Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.Cell discovery · 2025Article
- Role of shear stress-induced red blood cell released ATP in atherosclerosis.American journal of physiology. Heart and circulatory physiology · 2025Article
- Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review.Journal of molecular histology · 2025Review
- How selective antagonists and genetic modification have helped characterise the expression and functions of vascular P2Y receptors.Purinergic signalling · 2025Review
- Purinergic signaling in the battlefield of viral infections.Purinergic signalling · 2025Review
- Live Calcium Imaging on Mouse Primary Brain Endothelial Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevated blood pressure is a key risk factor for developing cardiovascular diseases. Blood pressure is largely determined by vasodilatory mediators, such as nitric oxide (NO), that are released from the endothelium in response to fluid shear stress exerted by the flowing blood. Previous work has identified several mechanotransduction signaling processes that are involved in fluid shear stress-induced endothelial effects, but how fluid shear stress initiates the response is poorly understood. Here, we evaluated human and bovine endothelial cells and found that the purinergic receptor P2Y2 and the G proteins Gq/G11 mediate fluid shear stress-induced endothelial responses, including [Ca2+]i transients, activation of the endothelial NO synthase (eNOS), phosphorylation of PECAM-1 and VEGFR-2, as well as activation of SRC and AKT. In response to fluid shear stress, endothelial cells released ATP, which activates the purinergic P2Y2 receptor. Mice with induced endothelium-specific P2Y2 or Gq/G11 deficiency lacked flow-induced vasodilation and developed hypertension that was accompanied by reduced eNOS activation. Together, our data identify P2Y2 and Gq/G11 as a critical endothelial mechanosignaling pathway that is upstream of previously described mechanotransduction processes and demonstrate that P2Y2 and Gq/G11 are required for basal endothelial NO formation, vascular tone, and blood pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.