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Store\u2010operated calcium entry is a prominent mode of calcium influx in endothelium. Store\u2010operated calcium entry channels are activated by inflammatory mediators and growth factors, and in endothelium, this process induces inter\u2010endothelial cell gaps that increase permeability. Pulmonary endothelium within extra\u2010alveolar segments, including pulmonary arteries, is especially sensitive to the activation of store\u2010operated calcium entry. Pulmonary arterial hypertension (PAH) is characterized by endothelial cell dysfunction in arteries. As one of the topics for the 2017 Grover Conference Series, we examined whether an endothelial cell permeability defect accompanies PAH and, if so, whether TRPC4 contributes to this defect. Through a series of studies conducted over the past five years, we find endothelial cell barrier dysfunction occurs early in the progression of experimental PAH. Endothelium within the arterial segment, and perhaps in other vascular segments, is highly susceptible to disruption secondary to both activation of store\u2010operated calcium entry channels and high flow. This phenomenon partly depends upon TRPC4 channels. We discuss whether endothelial cell hyperpermeability is relevant to human disease, and more specifically, whether it is relevant to all groups of pulmonary hypertension.<\/jats:p>","DOI":"10.1177\/2045894018798569","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T12:11:59Z","timestamp":1534767119000},"page":"1-9","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["The role of endothelial leak in pulmonary hypertension (2017 Grover Conference Series)"],"prefix":"10.1002","volume":"8","author":[{"given":"Chun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology University of South Alabama Mobile AL USA"},{"name":"Center for Lung Biology University of South Alabama Mobile AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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