Dynamic Changes in miR-21 Regulate Right Ventricular Dysfunction in Congenital Heart Disease-Related Pulmonary Arterial Hypertension

doi:10.3390/cells11030564

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標題:	Dynamic Changes in miR-21 Regulate Right Ventricular Dysfunction in Congenital Heart Disease-Related Pulmonary Arterial Hypertension
作者:	Chang, Wei-Ting Wu, Chia-Chun Lin, Yu-Wen Shih, Jhih-Yuan Chen, Zhih-Cherng Wu, Sheng-Nan Wu, Chia-Ching Hsu, Chih-Hsin
貢獻者:	Southern Taiwan University of Science & Technology National Cheng Kung University National Cheng Kung University Hospital Chi Mei Hospital Department of Pharmacy, Chia Nan University of Pharmacy & Science Department of Health and Nutrition, Chia Nan University of Pharmacy & Science National Cheng Kung University National Cheng Kung University Hospital Kaohsiung Medical University
關鍵字:	shear-stress microrna-21 echocardiography guidelines diagnosis
日期:	2022
上傳時間:	2023-12-11 13:57:47 (UTC+8)
出版者:	MDPI
摘要:	Right ventricular (RV) failure is a major cause of mortality in pulmonary arterial hypertension (PAH), but its mechanism remains largely unknown. MicroRNA-21 (miR-21) is involved in flow-mediated stress in the vasculature, but its effects on RV remodeling require investigations. Herein, we aim to study the mechanism of miR-21 in the early (compensated) and late (decompensated) phases of PAH-induced RV dysfunction. Using aorto-venous fistula (AVS) surgery, we established a rat model of PAH. To mimic the microenvironment of PAH, we treated cardiomyocytes with flow-mediated shear stress in 6 dyne for 3 and 8 h. To evaluate whether miR-21 could be a biomarker, we prospectively collected the sera of patients with congenital heart disease- (CHD) related PAH. Additionally, clinical, echocardiographic and right heart catheterization information was collected. The primary endpoint was hospitalization for decompensated heart failure (HF). It is of note that, despite an initial increase in miR-21 expression in hypertrophic RV post AVS, miR-21 expression decreased with RV dysfunction thereafter. Likewise, the activation of miR-21 in cardiomyocytes under shear stress at 3 h was downregulated at 6 h. The downregulated miR-21 at the late phase was associated with increased apoptosis in cardiomyocytes while miR-21 mimic rescued it. Among 76 CHD-induced PAH patients, 19 who were hospitalized for heart failure represented with a significantly lower expression of circulating miR-21. Collectively, our study revealed that the upregulation of miR-21 in the early phase (RV hypertrophy) and downregulation in the late phase (RV dysfunction) under PAH triggered a biphasic regulation of cardiac remodeling and cardiomyocyte apoptosis.
關聯:	Cells, v.11, n.3, pp.CC2, Article 564
顯示於類別:	[藥學系(所)] 期刊論文 [保健營養系(所) ] 期刊論文

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