Abstract
Aberrant vascular smooth muscle cell (VSMC) migration has been implicated in a variety of vascular disorders, while the signal pathways governing this process remain unclear. Here, we investigated whether miRNAs, which are strong post-transcriptional regulators of gene expression, could alter VSMC migration. We detected the expression of miR-4463 in the plasma of patients with atherosclerosis and in human aortic smooth muscle cells under hypoxia–ischemia condition, and investigated the migration effect and its downstream pathways. The results have shown that whether in clinical AS patients or hypoxic cells, the expression of miR-4463 was lower than that of normal group, then the number of migrating cells in the miR-4463 mimic intervention group was significantly decreased compared with the normal group and miR-4463 inhibitor instead. Furthermore, the expression of angiomotin (AMOT) in gastrocnemius muscle and femoral artery of patients was significantly higher than that of the control group. The protein level of AMOT in miR-4463 mimic intervention group was significantly decreased, and its level was reversed by inhibiting miR-4463. In summary, these results indicate that miR-4463 is a novel modulator of VSMC migration by targetting AMOT expression. Regulating miR-4463 or its specific downstream target genes in VSMCs may represent an attractive approach for the treatment of vascular diseases.
Highlights
Atherosclerosis is a chronic inflammatory disease, characterized by atherosclerotic plaques that cause hardening and narrowing of the lumen, which is the overwhelming cause of morbidity and mortality in the elderly patients in developed and developing countries [1]
Through a series of experiments, we found that, compared with the control group miR-4463 expression in sclerosis patients plasma and in human aortic smooth muscle cells (HASMCs) under hypoxia–ischemia condition was lower, and migrating cells number in miR-4463 mimic group was significantly decreased compared with the control group
Our results show that miR-4463 was obviously changed whether in arteriosclerosis obliterans (ASO) patients or in HASMCs under hypoxia–ischemia condition compared with respective control, which suggest that miR-4463 positively participate in the pathogenesis of ASO
Summary
Atherosclerosis is a chronic inflammatory disease, characterized by atherosclerotic plaques that cause hardening and narrowing of the lumen, which is the overwhelming cause of morbidity and mortality in the elderly patients in developed and developing countries [1]. In the early stage of atherosclerosis, vascular smooth muscle cells (VSMCs) migrate from the middle membrane to the inner wall of the arterial wall, abnormal proliferation and migration of VSMCs result in intimal thickening and narrowing at the end point [1,2]. MiRNAs are endogenous non-coding small RNAs that can post-transcriptionally regulate entire sets of genes [3,4], which play an important role in cell proliferation, apoptosis, and migration. Many miRNAs have been confirmed in regulating the migration of VSMCs through different target genes or pathways. Dong et al [6] confirmed that the target gene c 2018 The Author(s)
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