Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases.
Cardiovasc Toxicol
; 20(5): 463-473, 2020 10.
Article
in English
| MEDLINE | ID: covidwho-734059
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-ß-catenin, TGFß-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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cardiovascular Diseases
/
Ventricular Remodeling
/
MicroRNAs
/
Atrial Remodeling
/
Myocardium
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Cardiovasc Toxicol
Journal subject:
Vascular Diseases
/
Cardiology
/
Toxicology
Year:
2020
Document Type:
Article
Affiliation country:
S12012-020-09603-4
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