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There are no drugs currently available that are able to efficiently and safely inhibit this axis. We hypothesised that plumbagin (PLB), a natural organic compound known to block STAT3 in cancer cells, would reverse experimental pulmonary hypertension.<\/jats:p><jats:p>Using human PAH-PASMC, we demonstrated<jats:italic>in vitro<\/jats:italic>that PLB inhibits the activation of the STAT3\/NFAT axis, increasing the voltage-gated K<jats:sup>+<\/jats:sup>current bone morphogenetic protein receptor type II (BMPR2), and decreasing intracellular Ca<jats:sup>2+<\/jats:sup>contentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>), rho-associated coiled-coil containing protein kinase (ROCK)1 and interleukin (IL)-6, contributing to the inhibition of PAH-PASMC proliferation and resistance to apoptosis (proliferating cell nuclear antigen (PCNA), TUNEL, Ki67 and anexine V).<jats:italic>In vivo<\/jats:italic>, PLB oral administration decreases distal pulmonary artery remodelling, mean pulmonary artery pressure and right ventricular hypertrophy without affecting systemic circulation in both monocrotaline- and sugen\/chronic hypoxia-induced PAH in rats.<\/jats:p><jats:p>This study demonstrates that the STAT3\/NFAT axis can be therapeutically targeted by PLB in human PAH-PASMC and experimental PAH rat models. Thus, PLB could be considered a specific and attractive future therapeutic strategy for PAH.<\/jats:p>","DOI":"10.1183\/09031936.00084211","type":"journal-article","created":{"date-parts":[[2012,4,11]],"date-time":"2012-04-11T01:07:11Z","timestamp":1334106431000},"page":"618-629","source":"Crossref","is-referenced-by-count":63,"title":["Plumbagin reverses proliferation and resistance to apoptosis in experimental PAH"],"prefix":"10.1183","volume":"40","author":[{"given":"Audrey","family":"Courboulin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Barrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Perreault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique L.","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Paulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c8ve","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H.","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra N.","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steeve","family":"Provencher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2012,4,10]]},"reference":[{"key":"2024102021062651000_40.3.618.1","doi-asserted-by":"crossref","unstructured":"van de Veerdonk MC Kind T Marcus JT . 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