{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:30:49Z","timestamp":1790069449800,"version":"4.0.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-66299"],"award-info":[{"award-number":["HL-66299"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:p> Pulmonary microvascular endothelial cells (PMVECs) display a rapid angioproliferative phenotype, essential for maintaining homeostasis in steady-state and promoting vascular repair after injury. Although it has long been established that endothelial cytosolic Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) transients are required for proliferation and angiogenesis, mechanisms underlying such regulation and the transmembrane channels mediating the relevant [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transients remain incompletely understood. In the present study, the functional role of the microvascular endothelial site-specific \u03b1<jats:sub>1G<\/jats:sub> T-type Ca<jats:sup>2+<\/jats:sup> channel in angiogenesis was examined. PMVECs intrinsically possess an in vitro angiogenic \u201cnetwork formation\u201d capacity. Depleting extracellular Ca<jats:sup>2+<\/jats:sup> abolishes network formation, whereas blockade of vascular endothelial growth factor receptor or nitric oxide synthase has little or no effect, suggesting that the network formation is a [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>-dependent process. Blockade of the T-type Ca<jats:sup>2+<\/jats:sup> channel or silencing of \u03b1<jats:sub>1G<\/jats:sub>, the only voltage-gated Ca<jats:sup>2+<\/jats:sup> channel subtype expressed in PMVECs, disrupts network formation. In contrast, blockade of canonical transient receptor potential (TRP) isoform 4 or TRP vanilloid 4, two other Ca<jats:sup>2+<\/jats:sup> permeable channels expressed in PMVECs, has no effect on network formation. T-type Ca<jats:sup>2+<\/jats:sup> channel blockade also reduces proliferation, cell-matrix adhesion, and migration, three major components of angiogenesis in PMVECs. An in vivo study demonstrated that the mice lacking \u03b1<jats:sub>1G<\/jats:sub> exhibited a profoundly impaired postinjury cell proliferation in the lungs following lipopolysaccharide challenge. Mechanistically, T-type Ca<jats:sup>2+<\/jats:sup> channel blockade reduces Akt phosphorylation in a dose-dependent manner. Blockade of Akt or its upstream activator, phosphatidylinositol-3-kinase (PI3K), also impairs network formation. Altogether, these findings suggest a novel functional role for the \u03b1<jats:sub>1G<\/jats:sub> T-type Ca<jats:sup>2+<\/jats:sup> channel to promote the cell\u2019s angiogenic potential via a PI3K-Akt signaling pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.00336.2018","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T20:05:50Z","timestamp":1547669150000},"page":"C353-C364","source":"Crossref","is-referenced-by-count":15,"title":["\u03b1<sub>1G<\/sub> T-type calcium channel determines the angiogenic potential of pulmonary microvascular endothelial cells"],"prefix":"10.1152","volume":"316","author":[{"given":"Zhen","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hairu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Dickerson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy A. 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