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Author Bi, Rui ♦ Bao, Chunrong ♦ Jiang, Lianyong ♦ Liu, Hao ♦ Yang, Yang ♦ Mei, Ju ♦ Ding, Fangbao
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ARTERIES ♦ HUMAN POPULATIONS ♦ HYPERTENSION ♦ HYPERTROPHY ♦ IN VITRO ♦ IN VIVO ♦ INHIBITION ♦ NITRIC OXIDE ♦ PHENOTYPE ♦ RATS ♦ RECEPTORS ♦ SIGNALS
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. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-05-01
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 460
Issue Number 2


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