Abstract
microRNAs (miRNAs or miRs) play important roles in modulating the occurrence and progression of atherosclerosis and acute coronary syndrome (ACS). Herein, this study aimed to investigate the possible role of miR-9 in the development of atherosclerosis. Initially, the differentially expressed genes associated with ACS were screened and miRNAs that regulate syndecan-2 (SDC2) were predicted using microarray analysis. Furthermore, the biological functions of miR-9 and SDC2 on aortic plaque area, proliferation of collagen fibers, Mac-3-labeled macrophages, inflammatory response, and levels of the focal adhesion kinase/extracellular signal-regulated kinase (FAK/ERK) signaling pathway-related proteins in atherosclerosis were evaluated after ectopic miR-9 expression or SDC2 depletion in ACS mice using oil red O staining, Masson’s trichrome staining, immunohistochemistry, and Western blot analysis, respectively. SDC2 was highly-expressed, while miR-9 was poorly-expressed in atherosclerosis. Additionally, miR-9 targeted SDC2 and negatively-regulated its expression. Up-regulation of miR-9 reduced aortic plaque area, the proliferation of collagen fibers, Mac-3-labeled macrophages and levels of IL-6, IL-1β, and TNF-α by suppressing SDC2 and the FAK/ERK signaling pathway, thereby ameliorating atherosclerosis in ACS mice. In conclusion, the current study provides evidence that miR-9 retards atherosclerosis by repressing SDC2 and the FAK/ERK signaling pathway, highlighting a new theoretical basis for the treatment of atherosclerosis.
Highlights
Acute coronary syndrome (ACS) is the most fatal form of ischemic heart disease, including ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina (Falk et al, 2013)
In order to further verify the expression of SDC2 in acute coronary syndrome (ACS), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine SDC2 expression in the PBMCs isolated from patients with ACS
The findings suggested that SDC2 level was elevated in PBMCs from patients with ACS (p < 0.05; Figure 1B)
Summary
Acute coronary syndrome (ACS) is the most fatal form of ischemic heart disease, including ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina (Falk et al, 2013). The main clinical presentations in ACS consist of acute myocardial infarction, unstable angina (Wang and Jin, 2020), chest pain, sweating, and nausea (Khan et al, 2013). Advanced atherosclerosis with thrombus is one of the main characteristics of ACS (Libby et al, 2019). Vascular endothelial cell injury is one of the leading causes of plaque erosion and thrombosis formation, which contributes to the incidence and progression of ACS and atherosclerosis (Zhu et al, 2011). It is critical to explore the molecular mechanism of underlying atherosclerosis for exploration of novel target for treatment of atherosclerosis
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