MicroRNA-21 regulates right ventricular remodeling secondary to pulmonary arterial pressure overload

Wei Ting Chang, Sudeshna Fisch, Seema Dangwal, Jahan Mohebali, Amy G. Fiedler, Michael Chen, Chih Hsin Hsu, Yanfei Yang, Yiling Qiu, Kevin M. Alexander, Frederick Y. Chen, Ronglih Liao

研究成果: Article同行評審

摘要

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

原文English
頁(從 - 到)106-114
頁數9
期刊Journal of Molecular and Cellular Cardiology
154
DOIs
出版狀態Published - 2021 五月

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 心臟病學與心血管醫學

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