title: MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production.
abstract: Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH.
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Rui
authors: R
authors: Bi
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Chunrong
authors: C
authors: Bao
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Lianyong
authors: L
authors: Jiang
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Hao
authors: H
authors: Liu
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
authors: Ju
authors: J
authors: Mei
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China. Electronic address: dbcar126@126.com.
authors: Fangbao
authors: F
authors: Ding
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D047495:PPAR gamma / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D018841:HSP90 Heat-Shock Proteins; C000594049:MIRN27 microRNA, rat; D035683:MicroRNAs; D047495:PPAR gamma; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial nitric oxide synthase; NO; PPARγ; Pulmonary artery hypertension; miR-27b