Abstract
BackgroundAspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; however, the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells’ (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin.MethodsThe TNF-α induced proliferation model of VSMCs was divided into different groups with or without aspirin. Cell proliferation was detected by EdU; Real-time PCR was used to detect the mRNA expression of miR-145, CD40, and Calponin, a VSMCs differentiation marker gene. Western blot was used to detect the protein expression of CD40; ELISA was used to determine the concentrations of the inflammatory cytokine IL-6 in cell supernatants.ResultsThe proliferation of VSMCs was stimulated by TNF-α and accompanied by decreased levels of Calponin. TNF-α also decreased the levels of miR-145 and increased the levels of CD40 and IL-6. Pretreatment with 20 μg/mL of aspirin in VSMCs could partially block the above-mentioned effects induced by TNF-α. The protective effects of ASA in VSMCs were reversed by a pretreatment with a miR-145 inhibitor. We also found that the expression of miR-145 in peripheral blood mononuclear cells in ischemic stroke patients was significantly increased after a 10-day treatment with aspirin.ConclusionmiR-145 is involved in the anti-proliferation and anti-inflammation effects of aspirin on VSMCs by inhibiting the expression of CD40.
Highlights
Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood
MiR‐145 mediates the effect of aspirin on CD40 expression induced by TNF‐α The levels of miR-145 and CD40 mRNA expression in vascular smooth muscle cells’ (VSMCs) were determined by real-time PCR
Treatment of VSMCs with TNF-α significantly decreased the mRNA expression of miR-145 and increased the mRNA expression of CD40; whereas aspirin partially restored the mRNA level of miR-145 accompanied by a decrease in the mRNA level of CD40 compared to the TNF-α group
Summary
Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells’ (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin. Atherosclerosis (AS) is the pathological basis of coronary heart disease and ischemic stroke (IS), which is characterized by abnormal proliferation of vascular smooth muscle cells (VSMCs) [1, 2]. MiRNAs partially bind to complementary target sites in mRNA at the 3′UTR to regulate gene expression. Jakob and his colleagues have reported that miR-145 regulates VSMCs phenotype by targeting Krüppel-like factor 5 (KLF5) and helps control vascular neointimal lesion formation [3]. Other target genes, including Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) and tripartite motif containing 2 (TRIM2), have been identified as being controlled by miR-145 in cancer [8, 9]
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