Abstract
Atherosclerosis (AS) is a dynamic and multi-stage process that involves various cells types, such as vascular smooth muscle cells (VSMCs) and molecules such as microRNAs. In this study, we investigated how miR-338-3p works in the process of AS. To determine how miR-338-3p was expressed in AS, an AS rat model was established and primary rat VSMCs were cultured. Real-time polymerase chain reaction was performed to detect miR-338-3p expression. Markers of different VSMC phenotypes were tested by Western blot. Immunofluorescent staining was employed to observe the morphologic changes of VSMCs transfected with miR-338-3p mimics. A dual luciferase reporter assay system was used to verify that desmin was a target of miR-338-3p. To further identify the role of miR-338-3p in the development of AS, VSMC proliferation and migration were evaluated by EdU incorporation assay, MTT assay, and wound healing assay. miR-338-3p expression was upregulated in the aortic tissues of an AS rat model and in primary rat VSMCs from a later passage. The transfection of miR-338-3p mimics in VSMCs promoted the synthetic cell phenotype. Bioinformatics analysis proposed desmin as a candidate target for miR-338-3p and the dual luciferase reporter assay confirmed in vivo that desmin was a direct target of miR-338-3p. The MTT and EdU incorporation assay revealed increased cell viability when miR-338-3p mimics were transfected. The increased expression of PCNA was a consistent observation, although a positive result was not obtained with respect to VSMC mobility. In AS, miR-338-3p expression was elevated. Elevated miR-338-3p inhibited the expression of desmin, thus promoting the contractile-to-synthetic VSMC phenotypic transition. In addition to morphologic changes, miR-338-3p enhanced the proliferative but not mobile ability of VSMCs. In summary, miR-338-3p promotes the development of AS.
Highlights
In cardiovascular diseases, atherosclerosis (AS) is the main cause of morbidity and mortality [1]
During the development of the human body, vascular smooth muscle cells (VSMCs) primarily exist in two different phenotypes: 1 3 Vol:.(1234567890)
Compared with wild-type and A poE−/− rats that were fed with a normal diet (ND; Fig. 1), miR-338-3p was markedly elevated in tissues obtained from ApoE−/− rats fed a high-fat diet (HFD), and the relative expression of miR-338-3p was 1.51 ± 0.15 versus 0.67 ± 0.14(wild-type), 1.51 ± 0.15 versus 0. 83 ± 0.15(ApoE−/−),respectively
Summary
Atherosclerosis (AS) is the main cause of morbidity and mortality [1]. AS is a dynamic and multi-stage process, and includes dyslipidemia; an inflammatory response; endothelial cell (EC) dysfunction; vascular. A variety of cell types participate in the initiation and progression of AS, including inflammatory cells, ECs, and VSMCs. During the development of the human body, VSMCs primarily exist in two different phenotypes:. Synthetic VSMCs predominate in the embryonic and neonatal periods with active proliferative capacity; while contractile VSMCs are mainly found in adults and deprived of their ability to proliferate [7,8,9,10]. VSMC proliferation is part of the initiation and the progression of AS [13]. When stimulated by a dysfunctional endothelium and inflammatory factors, VSMCs differentiate, proliferate, and migrate into intima [14, 15]. At the fatty streak stage, VSMCs begin to differentiate into foam cells [6]
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