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• W3013260923 abstract "ABSTRACT Endothelial dysfunction contributes to the vascular pathology in pulmonary arterial hypertension (PAH). Circulating levels of endothelial miR-150 are reduced in PAH and act as an independent predictor of patient survival. The role of endothelial miR-150 in vascular dysfunction in PAH is not well understood. Endothelium-targeted miR-150 delivery prevented the disease in Sugen/hypoxia mice, while endothelial knockdown of miR-150 had adverse effects. miR-150 target genes revealed significant associations with PAH pathways, including proliferation, inflammation and phospholipid signaling, with PTEN-like mitochondrial phosphatase (PTPMT1) most markedly altered. PTPMT1 reduced inflammation, apoptosis and improved mitochondrial function in human pulmonary endothelial cells and blood-derived endothelial colony forming cells (ECFCs) from idiopathic PAH. Beneficial effects of miR-150 in vitro and in vivo were linked with PTPMT1-dependent biosynthesis of mitochondrial phospholipid cardiolipin and reduced expression of pro-apoptotic, pro-inflammatory and pro-fibrotic genes, including c-MYB, NOTCH3, TGF-β and Col1a1 . In conclusion, we are first to show that miR-150-PTPMT1-cardiolipin pathway attenuates pulmonary endothelial damage induced by vascular stresses and may be considered as a potential therapeutic strategy in PAH." @default.
• W3013260923 created "2020-04-03" @default.
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• W3013260923 date "2020-03-25" @default.
• W3013260923 modified "2023-10-16" @default.
• W3013260923 title "Role of endothelial microRNA-150 in pulmonary arterial hypertension" @default.
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• W3013260923 doi "https://doi.org/10.1101/2020.03.25.007021" @default.
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