Chang Wei-Ting, Hsu Chih-Hsin, Huang Tzu-Ling, Tsai Ying-Ching, Chiang Chun-Yen, Chen Zhih-Cherng, Shih Jhih-Yuan
Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center.
Department of Biotechnology, Southern Taiwan University of Science and Technology.
Acta Cardiol Sin. 2018 Nov;34(6):511-517. doi: 10.6515/ACS.201811_34(6).20180613A.
The outcome of pulmonary hypertension (PH) mainly depends on the development of right ventricular (RV) dysfunction, and survival among patients with different etiologies of PH varies. Chronic hypoxia is a major cause of secondary PH, however the mechanisms of its associated RV dysfunction are largely unknown. Herein, we studied the role of microRNA-21 (miR-21) in hypoxia-induced RV dysfunction.
In this longitudinal, prospective study, we enrolled 41 patients with hypoxia-induced PH. Echocardiography was conducted and circulating miR-21 was measured. The expression of miR-21 was also evaluated in hypoxia-treated human pulmonary microvascular endothelial cells (HPECs) and conditioned media. Through the over-expression of miR-21 in H9C2 cells, we further identified crosstalk between the pulmonary circulation and RV.
Among the studied patients, 10 developed RV dysfunction. Notably, the expression of circulating miR-21 was correlated with the severity of RV dysfunction. Likewise, miR-21 was up-regulated in the hypoxia-treated HPECs and its conditioned media in a time-dependent manner. I addition, hypertrophic changes were observed in the hypoxia-treated HPECs. The up-regulation of heart failure-associated markers in H9C2 cells over-expressing miR-21 implied the influence of pulmonary circulatory miR-21 on RV function.
The expression of systemic and pulmonary miR-21 is associated with the severity of RV dysfunction in patients with hypoxia-induced PH.
肺动脉高压（PH）的预后主要取决于右心室（RV）功能障碍的发展，且不同病因的PH患者生存率有所不同。慢性缺氧是继发性PH的主要原因，然而其相关RV功能障碍的机制尚不清楚。在此，我们研究了微小RNA-21（miR-21）在缺氧诱导的RV功能障碍中的作用。
在这项纵向、前瞻性研究中，我们纳入了41例缺氧诱导的PH患者。进行了超声心动图检查并测量了循环miR-21。还在缺氧处理的人肺微血管内皮细胞（HPECs）和条件培养基中评估了miR-21的表达。通过在H9C2细胞中过表达miR-21，我们进一步确定了肺循环与RV之间的相互作用。
在研究的患者中，10例出现了RV功能障碍。值得注意的是，循环miR-21的表达与RV功能障碍的严重程度相关。同样，miR-21在缺氧处理的HPECs及其条件培养基中呈时间依赖性上调。此外，在缺氧处理的HPECs中观察到肥大变化。过表达miR-21的H9C2细胞中与心力衰竭相关标志物的上调暗示了肺循环miR-21对RV功能的影响。
全身和肺miR-21的表达与缺氧诱导的PH患者RV功能障碍的严重程度相关。
