Role of miR96 in Pulmonary Arterial Hypertension

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Pulmonary arterial hypertension (PAH) is a devasting disease with a very poor survival rate. It occurs more frequently in women and involves the closing down of lung arteries due to thickening of their walls (remodelling). This puts a strain on the heart and causes failure of the right ventricle of the heart and death. Serotonin is a chemical that can cause this remodelling and it acts via a protein called a 5HT1B receptor. Small pieces of RNA called microRNAs can regulate genes and microRNA96 can decrease the number of 5HT1B receptors thus reducing the disease-causing effects of serotonin. In lung cells from female PAH patients or animal models, there can be a deficiency in this microRNA96 which causes an increase in the number of 5HT1B receptors. We have shown that restoring the levels of microRNA96 in lung arteries using a microRNA96 'mimic' by injection can decrease the number of 5HT1B receptors and can reverse pulmonary hypertension in mouse and rat models of the disease. Here we wish to understand fully how this mimic works. We will also determine the best way to administer the mimic, the best dose, if it has side effects and if it would work better with other drugs.