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Mol Ther Nucleic Acids. 2020 Sep 06;22:396-405. doi: 10.1016/j.omtn.2020.09.002. eCollection 2020 Dec 04.

Direct Delivery of MicroRNA96 to the Lungs Reduces Progression of Sugen/Hypoxia-Induced Pulmonary Hypertension in the Rat.

Molecular therapy. Nucleic acids

Craig K Docherty, Nina Denver, Simon Fisher, Margaret Nilsen, Dianne Hillyard, Rebecca L Openshaw, Hicham Labazi, Margaret R MacLean

Affiliations

  1. Strathclyde Institute of Pharmacy and Biological Sciences, University of Strathclyde, Glasgow G4 0RE, Scotland.
  2. Institute of Cardiovascular and Medical Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Scotland.

PMID: 33230444 PMCID: PMC7533346 DOI: 10.1016/j.omtn.2020.09.002

Abstract

The 5HT1B receptor (5HT1BR) contributes to the pathogenic effects of serotonin in pulmonary arterial hypertension. Here, we determine the effect of a microRNA96 (miR96) mimic delivered directly to the lungs on development of severe pulmonary hypertension in rats. Female rats were dosed with sugen (30 mg/kg) and subjected to 3 weeks of hypobaric hypoxia. In normoxia, rats were dosed with either a 5HT1BR antagonist SB216641 (7.5 mg/kg/day for 3 weeks), miR96, or scramble sequence (50 μg per rat), delivered by intratracheal (i.t) administration, once a week for 3 weeks. Cardiac hemodynamics were determined, pulmonary vascular remodeling was assessed, and gene expression was assessed by qRT-PCR, and

© 2020 The Authors.

Keywords: microRNA96; pulmonary hypertension; serotonin

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