摘要
肺高壓之預後主要和其造成之右心衰竭有關。慢性缺氧是造成肺高壓的原因之一，然而其造成右心衰竭的機轉目前仍未明。微型核糖核酸廣泛存在生物體中，負責基因轉錄後之修飾。在本研究中致力於探討微型核糖核酸–21 (microRNA–21; miR–21)在缺氧造成肺高壓之調控角色。我們收錄了四十一位缺氧導致肺高壓之患者，其中十位出現右心衰竭。此外，其血液中之微型核糖核酸–21的表現量也和右心衰竭呈正相關。此外，經缺氧刺激後人肺微血管内皮细胞(human pulmonary endothelial cell; HPEC)以及其條件培養基(conditioned medium)中，微型核糖核酸–21的表現也顯著地上升。更進一步，微型核糖核酸–21過度活化的心肌肌原細胞也出現肥大，以及心衰竭相關蛋白表現增加之情況。透過此結果，可以推想—經過缺氧刺激後，肺循環中增加的微型核糖核酸–21可能對右心心肌功能產生負面影響。
關鍵詞：缺氧造成之肺高壓、右心衰竭、微型核糖核酸–21
Abstract
The outcome of pulmonary hypertension (PH) mainly depends on the development of right ventricular (RV) dysfunction. Chronic hypoxia is a major cause of secondary PH; however, the mechanisms of its associated RV dysfunction are largely unknown. In this study, we aim to understand the role of microRNA–21 (miR–21) in hypoxia induced RV dysfunction. We enrolled 41 patients with hypoxia induced PH. Echocardiography was conducted and the circulating miR–21 was measured. Moreover, miR–21 expression was detected in hypoxia treated human pulmonary microvascular endothelial cells (human pulmonary endothelial cell; HPEC) and its conditioned media. Through over–expressing miR–21 in H9C2 cells, we further identified the crosstalk between the pulmonary circulation and RV. Among the studied patients, 10 developed RV dysfunction. It is noteworthy that the expression of circulating miR–21 was correlated with the severity of RV dysfunction. Similarly, miR–21 was up–regulated in the hypoxia treated HPEC and its conditioned media in a time–dependent manner. Furthermore, hypertrophic changes were observed in the hypoxia treated HPEC. The up–regulation of heart failure associated markers in miR–21 over–expressed myoblast (H9C2) cells suggested that pulmonary circulatory miR–21 could have influence on the RV function. As a result, we came to the conclusion that the expression of systemic and pulmonary miR–21 is associated with the severity of right ventricular dysfunction in patients with hypoxia induced pulmonary hypertension.
Keywords: Hypoxia Induced Pulmonary Hypertension, Right Ventricular Dysfunction, miR–21