Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases

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.

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

“…Other molecules were differently regulated in female and male mice hearts by ponatinib treatment, and, among these, our focus was on those related to Cx43. Namely, signal-regulated kinase (ERK), kinase B (Akt), microRNA122 (miR-122), and interleukin-6 (IL-6) were analyzed [ 14 , 15 , 16 , 17 ].…”

“…Akt and ERK were upregulated, while miR-122 was downregulated. This miRNA appears to be directly implicated in the development of cardiovascular diseases and its inhibition plays antifibrotic, anti-apoptotic, anti-inflammatory, and antioxidant functions [ 16 ]. MiR-122 could be linked to Cxs for their own involvement in miRNA intercellular transfer [ 15 ].…”

Correlation between serum miR-122 and myocardial damage and ventricular function in patients with essential hypertension

“…The severity of cardiovascular disease, including atherosclerosis, AMI, heart failure, atrial fibrillation and hypertension, is related to the expression of miR-122 expression. MiR-122 is also a risk factor of these cardiovascular diseases (32). MiR-122 could regulate autophagy, apoptosis, fibrosis, inflammatory reaction and dysfunction in cardiovascular system (33)(34)(35)(36).…”

Exosomes: Potential Player in Endothelial Dysfunction in Cardiovascular Disease

“…In addition, the exosome containing Rac-1 via the NOX 2/ROS/P38MAPK signaling pathway can lead to mitochondrial dysfunction, which is followed by caspase activation; it can induce apoptosis in ECs [ 94 ]. The exosome containing miR-122 can also play effective role in apoptosis induction in ECs by regulating the XIAP/ERK/Caspase8/Caspase3, GATA4/Bax/Bcl-2 and PTEN/PI3K/Akt signaling pathways [ 95 ].…”