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Abnormal activation of platelet\u2010derived growth factor signaling pathway through platelet\u2010derived growth factor receptors may contribute to the development and progression of pulmonary vascular remodeling and obliterative vascular lesions in patients with pulmonary arterial hypertension. In this study, we examined the expression of platelet\u2010derived growth factor receptor isoforms in pulmonary arterial smooth muscle and pulmonary arterial endothelial cells and investigated whether platelet\u2010derived growth factor secreted from pulmonary arterial smooth muscle cell or pulmonary arterial endothelial cell promotes pulmonary arterial smooth muscle cell proliferation. Our results showed that the protein expression of platelet\u2010derived growth factor receptor \u03b1 and platelet\u2010derived growth factor receptor \u03b2 in pulmonary arterial smooth muscle cell was upregulated in patients with idiopathic pulmonary arterial hypertension compared to normal subjects. Platelet\u2010derived growth factor activated platelet\u2010derived growth factor receptor \u03b1 and platelet\u2010derived growth factor receptor \u03b2 in pulmonary arterial smooth muscle cell, as determined by phosphorylation of platelet\u2010derived growth factor receptor \u03b1 and platelet\u2010derived growth factor receptor \u03b2. The platelet\u2010derived growth factor\u2010mediated activation of platelet\u2010derived growth factor receptor \u03b1\/platelet\u2010derived growth factor receptor \u03b2 was enhanced in idiopathic pulmonary arterial hypertension\u2010pulmonary arterial smooth muscle cell compared to normal cells. Expression level of platelet\u2010derived growth factor\u2010AA and platelet\u2010derived growth factor\u2010BB was greater in the conditioned media collected from idiopathic pulmonary arterial hypertension\u2010pulmonary arterial endothelial cell than from normal pulmonary arterial endothelial cell. Furthermore, incubation of idiopathic pulmonary arterial hypertension\u2010pulmonary arterial smooth muscle cell with conditioned culture media from normal pulmonary arterial endothelial cell induced more platelet\u2010derived growth factor receptor \u03b1 activation than in normal pulmonary arterial smooth muscle cell. Accordingly, the conditioned media from idiopathic pulmonary arterial hypertension\u2010pulmonary arterial endothelial cell resulted in more pulmonary arterial smooth muscle cell proliferation than the media from normal pulmonary arterial endothelial cell. These data indicate that (a) the expression and activity of platelet\u2010derived growth factor receptor are increased in idiopathic pulmonary arterial hypertension\u2010pulmonary arterial smooth muscle cell compared to normal pulmonary arterial smooth muscle cell, and (b) pulmonary arterial endothelial cell from idiopathic pulmonary arterial hypertension patients secretes higher level of platelet\u2010derived growth factor than pulmonary arterial endothelial cell from normal subjects. The enhanced secretion (and production) of platelet\u2010derived growth factor from idiopathic pulmonary arterial hypertension\u2010pulmonary arterial endothelial cell and upregulated platelet\u2010derived growth factor receptor expression (and function) in idiopathic pulmonary arterial hypertension\u2010pulmonary arterial smooth muscle cell may contribute to enhancing platelet\u2010derived growth factor\/platelet\u2010derived growth factor receptor\u2010associated pulmonary vascular remodeling in pulmonary arterial hypertension.<\/jats:p>","DOI":"10.1177\/2045894020948470","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T17:28:47Z","timestamp":1595611727000},"page":"1-15","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Endothelial platelet\u2010derived growth factor\u2010mediated activation of smooth muscle platelet\u2010derived growth factor receptors in pulmonary 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