title: MicroRNA Delivery Strategies to the Lung in a Model of Pulmonary Hypertension.
abstract: Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells and endothelial cells associated with obliteration of small pulmonary arterioles and formation of plexiform lesions. To date, no curative treatments have been identified for pulmonary arterial hypertension. There are various therapeutic options, including conventional medical therapies and oral, subcutaneous, intravenous, and inhalation delivery. We have previously shown that miR-143/145 knockout can prevent the development of chronic hypoxia-induced pulmonary hypertension (PH) in mice. Here, we use chronic hypoxia-induced PH as a disease model to evaluate miR-143/145 inhibition after delivery of antimiRNAs via the subcutaneous or intranasal routes. We use qRT-PCR and immunofluorescence to confirm that both delivery strategies efficiently inhibit miR-143/145 in lung tissue from mice with chronic hypoxia-induced PH.
authors.affiliation: Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.|Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 LittleFrance Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.|Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 LittleFrance Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
authors.affiliation: Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK. Angela.Bradshaw@glasgow.ac.uk.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Bradshaw
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000070416:Antagomirs / Q000008:administration & dosage; D002232:Carbocyanines / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000628:therapy*; D017380:Hypertrophy, Right Ventricular / Q000175:diagnosis; D000860:Hypoxia / Q000150:complications; D008168:Lung / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000070416:Antagomirs; D002232:Carbocyanines; D035683:MicroRNAs; C089187:cyanine dye 3
keywords: Anti-miR-143/145; Delivery; Hypoxia; Intranasal; MicroRNA; Pulmonary hypertension; Subcutaneous