Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary Hypertension

PloS One
Igor B GubrijLarry G Johnson

Abstract

Animals models have played an important role in enhancing our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). Dysregulation of the profile of microRNAs (miRNAs) has been demonstrated in human tissues from PAH patients and in animal models. In this study, we measured miRNA levels in the monocrotaline (MCT) rat model of PAH and examined whether blocking a specific dysregulated miRNA not previously reported in this model, attenuated PAH. We also evaluated changes in miRNA expression in lung specimens from MCT PAH rats overexpressing human prostacyclin synthase, which has been shown to attenuate MCT PAH. Expression levels of a panel of miRNAs were measured in MCT-PAH rats as compared to naïve (saline) control rats. Subsequently, MCT PAH rats were injected with a specific inhibitor (antagomiR) for miR-223 (A223) or a nonspecific control oligonucleotide (A-control) 4 days after MCT administration, then weekly. Three weeks later, RV systolic pressure and RV mass were measured. Total RNA, isolated from the lungs, microdissected pulmonary arteries, and right ventricle, was reverse transcribed and real-time quantitative PCR was performed. MiRNA levels were also measured in RNA isolated from paraffin sections o...Continue Reading

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Citations

Jul 30, 2019·Hypertension·Amela JusicUNKNOWN EU-CardioRNA COST Action (CA17129)
Apr 28, 2017·Cellular and Molecular Life Sciences : CMLS·Mar OrriolsPeter Ten Dijke
May 26, 2017·Current Hypertension Reports·Emile LevyJean-Michel Borys
Aug 16, 2019·International Journal of Molecular Sciences·Giuseppe MurdacaSebastiano Gangemi
Sep 29, 2017·Cardiovascular Research·Sandor BatkaiThomas Thum
Dec 19, 2020·Molecular Therapy. Nucleic Acids·Giusy RussomannoBeata Wojciak-Stothard
Dec 9, 2020·International Journal of Molecular Sciences·William Gerthoffer
Jun 3, 2021·Antioxidants·Daria S Kostyunina, Paul McLoughlin

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