Jul 11, 2014

Role of endothelial microRNA-150 in pulmonary arterial hypertension

BioRxiv : the Preprint Server for Biology
Anne-Christine MupepeleBeata Wojciak-Stothard

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 b...Continue Reading

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Mentioned in this Paper

Study
Health Services
Evaluation
Health Evaluation
Plea
Disease Management
Case-Control Studies
Research Design

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