ArticleScience signaling2014
AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Banxia baizhu tianma decoction, a Chinese herbal formula, for hypertension: Integrating meta-analysis and network pharmacology.Frontiers in pharmacology · 2022Pooled it
- Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease.Acta physiologica (Oxford, England) · 2026Review
- Decreased Transient Receptor Potential Channel mRNA Expression in the Aortas of Patients with Hypertension.Anatolian journal of cardiology · 2026Article
- TRPV4/IP3R-1-mediated endothelial pyroptosis drives pulmonary microvascular endothelial permeability in endotoxin-induced acute lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Elastin Regulation of Vasoreactivity in Resistance Arteries.Hypertension (Dallas, Tex. : 1979) · 2025Article
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Paracrine Smooth Muscle-to-Endothelial Signaling via TNF Elevates Blood Pressure in Obesity.Circulation research · 2025Article
- Investigating the Role of TRPV4 and GPR35 Interaction in Endothelial Dysfunction in Aging Mice.Aging cell · 2025Article
- Transient Receptor Potential Channels in Vascular Mechanotransduction.American journal of hypertension · 2025Review
- Activation of Piezo1 and TRPV4 channels contributes to hCMEC/D3 cell mechano-sensing.Frontiers in physiology · 2025Article
- Increased TRPV4 Channel Expression Enhances and Impairs Blood Vessel Function in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- CaInflammation and regeneration · 2024Review
- The life cycle of a capillary: Mechanisms of angiogenesis and rarefaction in microvascular physiology and pathologies.Vascular pharmacology · 2024Review
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress.Aging cell · 2024Article
- Mechanosensing by Vascular Endothelium.Annual review of physiology · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rather than by a global increase in endothelial cell Ca(2+). We showed that stimulation of muscarinic acetylcholine receptors on endothelial cells of mouse arteries exclusively activated TRPV4 channels that were localized at myoendothelial projections (MEPs), specialized regions of endothelial cells that contact smooth muscle cells. Muscarinic receptor-mediated activation of TRPV4 depended on protein kinase C (PKC) and the PKC-anchoring protein AKAP150, which was concentrated at MEPs. Cooperative opening of clustered TRPV4 channels specifically amplified Ca(2+) influx at MEPs. Cooperativity of TRPV4 channels at non-MEP sites was much lower, and cooperativity at MEPs was greatly reduced by chelation of intracellular Ca(2+) or AKAP150 knockout, suggesting that Ca(2+) entering through adjacent channels underlies the AKAP150-dependent potentiation of TRPV4 activity. In a mouse model of angiotensin II-induced hypertension, MEP localization of AKAP150 was disrupted, muscarinic receptor stimulation did not activate TRPV4 channels, cooperativity among TRPV4 channels at MEPs was weaker, and vasodilation in response to muscarinic receptor stimulation was reduced. Thus, endothelial-dependent dilation of resistance arteries is enabled by MEP-localized AKAP150, which ensures the proximity of PKC to TRPV4 channels and the coupled channel gating necessary for efficient communication from endothelial to smooth muscle cells in arteries. Disruption of this molecular assembly may contribute to altered blood flow in hypertension.
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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.