MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

Biochemical and Biophysical Research Communications
Rui BiFangbao Ding

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 Hsp...Continue Reading

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Citations

Nov 12, 2016·Current Hypertension Reports·Miruna NemeczAdriana Georgescu
Dec 19, 2016·Trends in Molecular Medicine·A A Roger Thompson, Allan Lawrie
Jul 30, 2019·Hypertension·Amela JusicUNKNOWN EU-CardioRNA COST Action (CA17129)
Mar 16, 2017·JCI Insight·Vinny Negi, Stephen Y Chan
Jun 3, 2017·Cellular and Molecular Life Sciences : CMLS·Dewei ChenYuqi Gao
Dec 26, 2018·Antioxidants & Redox Signaling·Victor TsengC Michael Hart

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