{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:38:47Z","timestamp":1791113927158,"version":"4.1.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:p> An increase in cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for pulmonary arterial medial hypertrophy in patients with idiopathic pulmonary arterial hypertension (IPAH). Vascular smooth muscle cells (SMC) sense the blood flow shear stress through interstitial fluid driven by pressure or direct exposure to blood flow in case of endothelial injury. Mechanical stimulus can increase [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub>. Here we report that flow shear stress raised [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in PASMC, while the shear stress-mediated rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> and the protein expression level of TRPM7 and TRPV4 channels were significantly greater in IPAH-PASMC than in normal PASMC. Blockade of TRPM7 by 2-APB or TRPV4 by Ruthenium red inhibited shear stress-induced rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in normal and IPAH-PASMC, while activation of TRPM7 by bradykinin or TRPV4 by 4\u03b1PDD induced greater increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in IPAH-PASMC than in normal PASMC. The bradykinin-mediated activation of TRPM7 also led to a greater increase in [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in IPAH-PASMC than in normal PASMC. Knockdown of TRPM7 and TRPV4 by siRNA significantly attenuated the shear stress-mediated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> increases in normal and IPAH-PASMC. In conclusion, upregulated mechanosensitive channels (e.g., TRPM7, TRPV4, TRPC6) contribute to the enhanced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> increase induced by shear stress in PASMC from IPAH patients. Blockade of the mechanosensitive cation channels may represent a novel therapeutic approach for relieving elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyt<\/jats:sub> in PASMC and thereby inhibiting sustained pulmonary vasoconstriction and pulmonary vascular remodeling in patients with IPAH. <\/jats:p>","DOI":"10.1152\/ajpcell.00115.2014","type":"journal-article","created":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T08:55:35Z","timestamp":1402563335000},"page":"C373-C383","source":"Crossref","is-referenced-by-count":66,"title":["Flow shear stress enhances intracellular Ca<sup>2+<\/sup> signaling in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension"],"prefix":"10.1152","volume":"307","author":[{"given":"Shanshan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;"},{"name":"Departments of Medicine and Physiology, University of Arizona College of Medicine, 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