Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases
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Roles of MicroRNA‑122 in Cardiovascular Fibrosis and Related Diseases Ying Liu1,2 · Jia‑Wei Song1 · Jian‑Yu Lin3 · Ran Miao1,2 · Jiu‑Chang Zhong1,2 Received: 25 June 2020 / Accepted: 18 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Fibrotic diseases cause annually more than 800,000 deaths worldwide, where of the majority accounts for cardiovascular fibrosis, which is characterized by endothelial dysfunction, myocardial stiffening and reduced dispensability. MicroRNAs (miRs), small noncoding RNAs, play critical roles in cardiovascular dysfunction and related disorders. Intriguingly, there is a critical link among miR-122, cardiovascular fibrosis, sirtuin 6 (SIRT6) and angiotensin-converting enzyme 2 (ACE2), which was recently identified as a coreceptor for SARS-CoV2 and a negative regulator of the rennin-angiotensin system. MiR-122 overexpression appears to exacerbate the angiotensin II-mediated loss of autophagy and increased inflammation, apoptosis, extracellular matrix deposition, cardiovascular fibrosis and dysfunction by modulating the SIRT6-Elabela-ACE2, LGR4-β-catenin, TGFβ-CTGF and PTEN-PI3K-Akt signaling pathways. More importantly, the inhibition of miR-122 has proautophagic, antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic effects. Clinical and experimental studies clearly demonstrate that miR-122 functions as a crucial hallmark of fibrogenesis, cardiovascular injury and dysfunction. Additionally, the miR-122 level is related to the severity of hypertension, atherosclerosis, atrial fibrillation, acute myocardial infarction and heart failure, and miR-122 expression is a risk factor for these diseases. The miR-122 level has emerged as an early-warning biomarker cardiovascular fibrosis, and targeting miR-122 is a novel therapeutic approach against progression of cardiovascular dysfunction. Therefore, an increased understanding of the cardiovascular roles of miR-122 will help the development of effective interventions. This review summarizes the biogenesis of miR-122; regulatory effects and underlying mechanisms of miR-122 on cardiovascular fibrosis and related diseases; and its function as a potential specific biomarker for cardiovascular dysfunction. Keywords microRNA-122 · Fibrosis · Cardiovascular dysfunction · Sirtuin 6 · ACE2
Introduction Cardiovascular fibrosis, a vital cause of heart failure (HF), refers to the development of scar tissue in the injured heart and blood vessels due to an aberrant wound-healing response Communicated by Kurt J. Varner. * Ran Miao [email protected] * Jiu‑Chang Zhong [email protected] 1
Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020, China
2
Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
3
Department of Comprehensive Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
to injury or insult, and arises from enhanced inflammato
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