Endothelial pannexin 1-TRPV4 channel signaling lowers pulmonary arterial pressure in mice.
Zdravka Daneva,Matteo Ottolini,Yen Lin Chen,Eliska Klimentova,Maniselvan Kuppusamy,Soham A Shah,Richard D. Minshall,Cheikh I. Seye,Victor E. Laubach,Brant E. Isakson,Swapnil K. Sonkusare +10 more
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TLDR
In this paper, the authors showed that Panx1-P2Y2R-TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.Abstract:
Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates of endothelial TRPV4 channels. We hypothesized that endothelial Panx1-ATP-TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Ca (PKCa), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCa, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1-P2Y2R-TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.read more
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Journal ArticleDOI
Endothelial pannexin-1 channels modulate macrophage and smooth muscle cell activation in abdominal aortic aneurysm formation
Amanda C. Filiberto,Michael Spinosa,Craig T. Elder,Gang Su,Victoria Leroy,Zachary J. Ladd,Guanyi Lu,J. Hunter Mehaffey,Morgan Salmon,Robert B. Hawkins,Kodi S. Ravichandran,Brant E. Isakson,Gilbert R. Upchurch,Ashish Sharma +13 more
TL;DR: Pannexin-1 (Panx1) channels have been shown to regulate leukocyte trafficking and tissue inflammation but the mechanism of Panx1 in chronic vascular diseases like abdominal aortic aneurysms (AAA) is unknown as mentioned in this paper .
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Novel Smooth Muscle Ca <sup>2+</sup> -Signaling Nanodomains in Blood Pressure Regulation
TL;DR: In this article , the contribution of TRPV4SMC channels to the constrictor effect of α1 adrenergic receptor (α1AR) stimulation and elevated intraluminal pressure was determined.
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Vascular Mechanotransduction.
TL;DR: A review of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels, is presented in this article .
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TRPV4: A trigger of pathological RhoA activation in neurological disease
TL;DR: It is proposed that TRPV4 and the cytoskeletal remodeling small GTPase RhoA together constitute an environmentally sensitive signaling complex that contributes to pathological cell cytoskeleton alterations during neurological injury and disease.
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Small-world connectivity dictates collective endothelial cell signaling
Matthew D. Lee,Charlotte Buckley,Xu Zhang,Lauri M. Louhivuori,Per Uhlén,Calum Wilson,John G. McCarron +6 more
TL;DR: This work shows that the endothelium resolves the issue of distributed sensing by using a network with scale-free and small-world properties, which confers a high signal-propagation speed and a high degree of synchronizability across the endot Helium.
References
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Pannexin membrane channels are mechanosensitive conduits for ATP
TL;DR: Pannexin 1 channels have a wide expression spectrum, they are of large conductance and permeant for ATP, and they are mechanosensitive, Hence, pannexins are candidates for the release of ATP to the extracellular space upon mechanical stress.
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G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension.
Angela Wirth,Zoltán Benyó,Zoltán Benyó,Martina Lukasova,Barbara Leutgeb,Barbara Leutgeb,Nina Wettschureck,Stefan Gorbey,Petra Örsy,Béla Horváth,Christiane Maser-Gluth,Erich Greiner,Erich Greiner,Björn Lemmer,Günther Schütz,J. Silvio Gutkind,Stefan Offermanns +16 more
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Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium
TL;DR: It is shown that pannexin 1 channels can be activated by extracellular ATP acting through purinergic receptors of the P2Y group as well as by cytoplasmic calcium.
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