Wei-Ting Chang1,2, Chih-Hsin Hsu3, Tzu-Ling Huang1, Ying-Ching Tsai1, Chun-Yen Chiang1, Zhih-Cherng Chen1,4, Jhih-Yuan Shih1. 1. Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center. 2. Department of Biotechnology, Southern Taiwan University of Science and Technology. 3. Department of Intensive Care Medicine, Cheng Kung University Hospital. 4. Department of Pharmacy, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The expression of systemic and pulmonary miR-21 is associated with the severity of RV dysfunction in patients with hypoxia-induced PH.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The expression of systemic and pulmonary miR-21 is associated with the severity of RV dysfunction in patients with hypoxia-induced PH.
Entities:
Keywords:
Hypoxia-induced pulmonary hypertension; Right ventricular dysfunction; miR-21
Authors: Victoria N Parikh; Richard C Jin; Sabrina Rabello; Natali Gulbahce; Kevin White; Andrew Hale; Katherine A Cottrill; Rahamthulla S Shaik; Aaron B Waxman; Ying-Yi Zhang; Bradley A Maron; Jochen C Hartner; Yuko Fujiwara; Stuart H Orkin; Kathleen J Haley; Albert-László Barabási; Joseph Loscalzo; Stephen Y Chan Journal: Circulation Date: 2012-02-27 Impact factor: 29.690
Authors: Mohammed I Ahmed; Andrei N Mardaryev; Christopher J Lewis; Andrey A Sharov; Natalia V Botchkareva Journal: J Cell Sci Date: 2011-10-07 Impact factor: 5.285
Authors: Benoît Ranchoux; Lloyd D Harvey; Ramon J Ayon; Aleksandra Babicheva; Sebastien Bonnet; Stephen Y Chan; Jason X-J Yuan; Vinicio de Jesus Perez Journal: Pulm Circ Date: 2017-12-28 Impact factor: 3.017