ArticleThe Journal of clinical investigation2019
Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- The mechanisms of exercise improving cardiovascular function by stimulating Piezo1 and TRP ion channels: a systemic review.Molecular and cellular biochemistry · 2025Pooled it
- The dual role of capsaicin in inflammatory bowel disease: from TRPV1-mediated protection to neurogenic inflammation.Inflammopharmacology · 2026Review
- Mechanotransduction through oxidative stress upregulates circLyst to drive vascular remodeling in hypertensive humans and rodents.Molecular biomedicine · 2026Article
- Bioactive adrenomedullin dynamics and microcirculatory changes in a porcine model of hemorrhagic shock.Intensive care medicine experimental · 2026Article
- Decoding intervertebral disc degeneration pathomechanics: from mechanisms to therapeutic horizons.Journal of advanced research · 2026Review
- Article
- Characterizing the molecular landscape of venous congestion.World journal of critical care medicine · 2026Article
- PIEZO Channels in Metabolism and Metabolic Diseases: Research Advances and Therapeutic Strategies.Current obesity reports · 2026Review
- Decoding osteosarcoma mechanobiology: PIEZO channels in tumor progression, immune remodeling, and pain.Cancer metastasis reviews · 2026Review
- Piezo1 channel: structure, mechanogating mechanism, functions, diseases and therapeutic strategy.Molecular biomedicine · 2026Review
- Noninvasive biophysical modulations of Piezo ion channels.Microsystems & nanoengineering · 2026Review
- Article
- Pulsatility as a Potential Regulator of Cardiovascular Biology: Molecular, Cellular, and Hemodynamic Remodeling During Continuous-Flow Left Ventricular Assist Device Support and Following Heart Transplantation.International journal of molecular sciences · 2026Review
- Mediation effect of TyG-BMI, LDL-C, and CRP on physical activity-stroke risk relationship.Scientific reports · 2026Article
- Vascular mechanical forces and vascular diseases.Journal of advanced research · 2026Review
- Ultrasound-targeted microbubble cavitation enhances anti-PD-L1 therapy in TNBC via eNOS-mediated reoxygenation.JCI insight · 2026Article
- CaRPOOL: a pooled calcium‑recording CRISPR screening platform identifies CCR7 as a modulator of cellular osmomechanosensing.Cell communication and signaling : CCS · 2026Article
- Piezo1 in the central nervous system: decoding the mechanical signature of neuroinflammation.Journal of neuroinflammation · 2026Review
- Physical exercise protects cardiovascular fitness in long-term spaceflight: what have we learned?Science China. Life sciences · 2026Review
- Integrative network pharmacology and experimental study of Qingda granule in hypertension-induced endothelial dysfunction.Experimental animals · 2026Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
Hypertension is a primary risk factor for cardiovascular diseases including myocardial infarction and stroke. Major determinants of blood pressure are vasodilatory factors such as nitric oxide (NO) released from the endothelium under the influence of fluid shear stress exerted by the flowing blood. Several endothelial signaling processes mediating fluid shear stress-induced formation and release of vasodilatory factors have been described. It is, however, still poorly understood how fluid shear stress induces these endothelial responses. Here we show that the endothelial mechanosensitive cation channel PIEZO1 mediated fluid shear stress-induced release of adrenomedullin, which in turn activated its Gs-coupled receptor. The subsequent increase in cAMP levels promoted the phosphorylation of endothelial NO synthase (eNOS) at serine 633 through protein kinase A (PKA), leading to the activation of the enzyme. This Gs/PKA-mediated pathway synergized with the AKT-mediated pathways leading to eNOS phosphorylation at serine 1177. Mice with endothelium-specific deficiency of adrenomedullin, the adrenomedullin receptor, or Gαs showed reduced flow-induced eNOS activation and vasodilation and developed hypertension. Our data identify fluid shear stress-induced PIEZO1 activation as a central regulator of endothelial adrenomedullin release and establish the adrenomedullin receptor and subsequent Gs-mediated formation of cAMP as a critical endothelial mechanosignaling pathway regulating 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.