Role of miR96 in Pulmonary Arterial Hypertension

肺动脉高压（PAH）是一种生存率极低的毁灭性疾病。它在女性中更常见，并且涉及由于肺动脉壁增厚而导致的肺动脉关闭（重塑）。这会对心脏造成压力，导致心脏右心室衰竭和死亡。血清素是一种化学物质，可以引起这种重塑，它通过一种称为5 HT 1B受体的蛋白质起作用。称为microRNA的小片段RNA可以调节基因，microRNA 96可以减少5 HT 1B受体的数量，从而减少5-羟色胺的致病作用。在女性PAH患者或动物模型的肺细胞中，这种microRNA 96可能存在缺陷，导致5 HT 1B受体数量增加。我们已经证明，通过注射microRNA 96“模拟物”恢复肺动脉中microRNA 96的水平可以减少5 HT 1B受体的数量，并可以逆转小鼠和大鼠模型中的肺动脉高压。在这里，我们希望充分了解这种模仿是如何工作的。我们还将确定最佳的方式来管理模拟，最佳剂量，如果它有副作用，如果它会更好地与其他药物。

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.