Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases
Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases
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MicroRNA-122 在心血管纤维化及相关疾病中的作用
DOI：
10.1007/s12012-020-09603-4
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发表时间：
2020-08-27
影响因子：
3.2
通讯作者：
Zhong, Jiu-Chang
中科院分区：
文献类型：
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作者：
Liu, Ying;Song, Jia-Wei;Zhong, Jiu-Chang
纤维化疾病每年在全世界造成超过800，000例死亡，其中大部分是心血管纤维化，其特征在于内皮功能障碍、心肌硬化和可分配性降低。microRNAs（miRs）是一类非编码小分子RNA，在心血管功能障碍及相关疾病中发挥重要作用。有趣的是，在miR-122、心血管纤维化、sirtuin 6（SIRT 6）和血管紧张素转换酶2（ACE 2）之间存在关键联系，ACE 2最近被鉴定为SARS-CoV 2的共受体和肾素-血管紧张素系统的负调节剂。MiR-122过表达似乎通过调节SIRT 6-Elabela-ACE 2、LGR 4-β-连环蛋白、TGFβ-CTGF和PTEN-PI 3 K-Akt信号传导途径来加剧血管紧张素II介导的自噬丧失和增加的炎症、凋亡、细胞外基质沉积、心血管纤维化和功能障碍。更重要的是，抑制miR-122具有促自噬、抗氧化、抗炎、抗凋亡和抗纤维化作用。临床和实验研究清楚地表明，miR-122是纤维化、心血管损伤和功能障碍的重要标志。此外，miR-122水平与高血压、动脉粥样硬化、心房颤动、急性心肌梗死和心力衰竭的严重程度相关，并且miR-122表达是这些疾病的危险因素。miR-122水平已成为心血管纤维化的早期预警生物标志物，靶向miR-122是对抗心血管功能障碍进展的新治疗方法。因此，增加对miR-122在心血管作用的了解将有助于开发有效的干预措施。本文综述了miR-122的生物起源、miR-122对心血管纤维化及相关疾病的调控作用和机制，以及miR-122作为心血管功能障碍的潜在特异性生物标志物的功能。
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.