The role for miR-145 and miR-21 in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disease characterised by an increase in pulmonary arterial pressure and right ventricular (RV) hypertrophy. Current therapies for pulmonary hypertension are very limited and lack efficacy; 3 year survival rate is <60%. We are investigating whether the misregulation or misfunctioning of microRNAs (miRNAs) is responsible for the development of PAH. These microscopic fragments of RNA regulate one of the first steps in protein manufacture within the human body. We hope to develop new therapies that manipulate miRNA levels in order to treat pulmonary arterial hypertension.

We are interested in the role of miRNA-21 and miR-145 in the pathobiology of pulmonary arterial hypertension (PAH). miR-145 and miR-21 are dysregulated in mouse models of PAH. Downregulation of miR-145 protects against the development of PAH, whereas downregulation of miR-21 exaggerates the pathobiology of PAH. We hope to develop antimiR or adeno-associated virus therapeutics that specifically regulate miRNAs in the lung.

Publications

1. Caruso P, Dempsie Y, Stevens HC, McDonald RA, Long L, Lu R, White K, Mair KM, McClure JD, Southwood M, Upton P, Xin M, van Rooij E, Olson EN, Morrell NW, MacLean MR, Baker AH. A role for miR-145 in pulmonary arterial hypertension: Evidence from mouse models and patient samples, Circ Res. 2012; 111:290-300
2. Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, Denby L, Dempsie Y, Long L, Morrell NW, Baker AH. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol. 2010; 30:716-23