Regulatory Mechanism of MicroRNA-145 in the Pathogenesis of Acute Aortic Dissection

Abstract

PurposePrevious studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection (AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD.Materials and MethodsAAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Gene and protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferase reporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 in VSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability.ResultsmiR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients with AAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increased in aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF was confirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD.ConclusionmiR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide a potential therapeutic target for AAD.

The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease

“…In cardiovascular diseases, the miR-143/145 cluster is the best studied miRNA cluster. Indeed, miR-145 and miR-143 are widely involved in cardiovascular diseases, such as atherosclerosis, coronary heart disease, aortic dissection, valvular disease, and pulmonary hypertension ( Caruso et al, 2012 ; Liu et al, 2013 , 2019 ; Guo et al, 2016 ; Girdauskas et al, 2018 ; Shi et al, 2018 ; Sun et al, 2018 ; Yue et al, 2018 ; Li T. et al, 2019 ; Vacante et al, 2019 ). Deng et al (2015) reported that exosomal miR-143 regulates the interaction between VSMCs and endothelial cells in PAH.…”

Non‐coding RNAs in aortic dissection: From biomarkers to therapeutic targets

“…Another study reported that the miR‐145 expression level is consistent with the mortality of patients with AD. Increased miR‐145 expression can accelerate VSMC proliferation and ameliorate cell apoptosis by binding to SMAD3 and connective tissue growth factor (CTGF), which can reduce the effect of miR‐145 in the progression of AAD 20 . CTGF, a matricellular protein, can ameliorate aortic remodelling in the rat AD model and participate in the proliferation and apoptosis of VSMCs 68 .…”

“…Particularly, numerous studies have reported that non‐coding RNAs (ncRNAs) play a significant role in the development of cardiovascular diseases, such as atherosclerosis, restenosis after stent and aneurysm 14‐18 . Likewise, several reports have suggested that ncRNAs also play a crucial regulatory role in the occurrence and development of AD 19‐21 . In this review, we discuss the role of ncRNAs and their target genes, as well as their regulatory mechanisms in AD.…”

“…[14][15][16][17][18] Likewise, several reports have suggested that ncRNAs also play a crucial regulatory role in the occurrence and development of AD. [19][20][21] In this review, we discuss the role of ncRNAs and their target genes, as well as their regulatory mechanisms in AD. In this review, we highlight some previously identified ncRNAs that are involved in multiple processes that lead to AD.…”

Construction of a circRNA - Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection

“…Previously, several miRNAs have been con rmed to be closely involved in cardiovascular diseases and even maybe a new strategy for the diagnosis, therapy, or prediction in cardiovascular diseases. Certain miRNAs, such as miRNA-21 [7], miRNA-134-5p [8], miRNA-145 [9], miRNA-146b [10], have been reported to play de nite roles in the development of AD.…”