Abstract
Background: Multiple studies showed that long-chain noncoding RNA H19 (LncRNA H19) is high-expressed in human and mouse abdominal aortic aneurysms (AAAs). We speculated that it plays an important role in arterial disease, and therefore studied the role and mechanism of H19 in aortic dissection (AD).Methods: The expressions of related genes in human aortic smooth muscle cells (HASMCs) induced by platelet-derived growth factor BB (PDGF-BB) or in the aortic tissue of AD patients/mice were identified by Western blot and quantitative real-time polymerase chain reaction. The targeting relationship between H19 and miR-193b-3p was predicted and verified by bioinformatics analysis, dual luciferase assay, RNA pull-down assay, RNA immunoprecipitation (RIP), and Pearson correlation coefficient. The H19 and miR-193b-3p effects on the biological functions of tissues and cells were examined by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide) assay, wound-healing assay, and Hematoxylin–Eosin (HE) staining.Results: LncRNA H19 was abnormally high-expressed in thoracic aorta tissues of AD patients, and it could competitively bind to and inhibit miR-193b-3p. In the PDGF-BB group, the expressions of H19, matrix metallopeptidase (MMP) 2 (MMP-2) and MMP-9 were up-regulated and the expressions of miR-193b-3p, α-SMA, and SM22α were down-regulated; moreover, the proliferation and migration rate of HASMCs were increased. However, H19 silencing reversed the regulation of PDGF-BB on HASMCs. More interestingly, miR-193b-3p inhibitor could partially reverse the effect of H19 silencing. In addition, the above results were verified by animal experiments, showing that shH19 and up-regulated miR-193b-3p could significantly reduce the thoracic aorta pathological damage in AD mice.Conclusion: LncRNA H19 regulated smooth muscle cell function by sponging miR-193b-3p and it participated in the development of AD.
Highlights
Aortic rupture/dissection (AD) is caused by an intima-media tear in the aorta under the impact of high velocity and pressure blood flow, forming a false or true lumen [1]
LncRNA H19 was abnormally high-expressed in thoracic aorta tissues of aortic dissection (AD) patients, and could bind and inhibit miR-193b-3p
We again determined the expression of miR-193b-3p in the AD aorta samples and normal aortic samples, and found that miR-193b-3p expression was significantly lower in the AD group than the healthy group (P
Summary
Aortic rupture/dissection (AD) is caused by an intima-media tear in the aorta under the impact of high velocity and pressure blood flow, forming a false or true lumen [1]. Recent studies found that TAD is a comprehensive pathological change process caused by pathological changes involving multiple blood vessel constituents, such as human aortic smooth muscle cells (HASMCs) and extracellular matrix (ECM) [3,4]. Dedifferentiated VSMCs showed higher viability in terms of proliferation, migration and synthesis, and at the same time, the expressions of differentiation markers α-SMA and SM22α were down-regulated [6]. Multiple studies showed that long-chain noncoding RNA H19 (LncRNA H19) is high-expressed in human and mouse abdominal aortic aneurysms (AAAs). We speculated that it plays an important role in arterial disease, and studied the role and mechanism of H19 in aortic dissection (AD). Conclusion: LncRNA H19 regulated smooth muscle cell function by sponging miR-193b-3p and it participated in the development of AD
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