Abstract. Atherosclerosis and coronary heart disease are characterized by a hyperplastic neointima and inflammation involving cytokines, such as tumor necrosis factor-α (TNF-α). TNF-α is pleiotropic and mediates inflammation and proliferation in various cell types, such as vascular smooth muscle cells (VSMCs). The molecular mechanism for the pleiotropic effects of TNF-α has not previously been fully elucidated. The current study identified that the expression of microRNA-25 (miR-25), a small noncoding RNA, was reduced in response to TNF-α signaling in VSMCs. Restored miR-25 expression inhibited cell proliferation and Ki-67 expression. The present study indicated that cyclin-dependent kinase 6 (CDK6) was the direct target gene of miR-25 using mRNA and protein expression analysis, and luciferase assays. It was also observed that restored CDK6 expression in the miR-25 mimic-treated VSMCs partly reduced miR-25-mediated VSMC proliferation. In conclusion, miR-25 is suggested to be important in TNF-α-induced abnormal proliferation of VSMCs.
BackgroundGenetic variation of matrix metalloproteinase 9 (MMP-9) gene polymorphism has been suggested to modulate coronary heart diseases (CHD), yet the underlying mechanisms are not well understood.MethodsWe investigated the association of MMP9 rs3918242 single nucleotide polymorphism with inflammation and lipid-lowering efficacy after simvastatin treatment in Chinese patients with CHD. Fasting serum lipid profile and plasma inflammatory mediators were determined at baseline in 264 patients with CHD and 186 healthy control subjects, and after HMG-CoA reductase inhibitor simvastatin treatment (20 mg/day) for 12 weeks in CHD subjects.ResultsWe found that plasma MMP-9, TNF-α and IL-10 levels were significantly elevated in patients with CHD compared to control subjects before treatment. The plasma MMP9 in CHD patients carrying rs3918242 CC, CT and TT genotypes were comparable. Interestingly, CHD patients carrying TT genotype had significantly higher level of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) than those carrying CC genotype (P <0.05). Simvastatin treatment significantly reduced LDL-C, TG and plasma inflammatory mediator levels in CHD patients. The reduction of LDL-C upon simvastatin therapy was significantly greater in patients carrying TT genotype than those carrying CC genotype (P <0.05).ConclusionsMMP9 rs3918242 TT genotype is associated with elevated serum TG and LDL-C, and enhanced LDL-C-lowering response upon simvastatin treatment in Chinese patients with CHD.Clinical trial registrationThis study was retrospectively registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-ROC-17010971) on March 23rd 2017.
Myocardial infarction (MI) is a serious heart disease. The cardiac cells of patients with MI will die due to lack of blood for a long time. In this study, we aimed to find new targets for MI diagnosis and therapy. We downloaded GSE22229 including 12 blood samples from healthy persons and GSE29111 from Gene Expression Omnibus including 36 blood samples from MI patients. Then we identified differentially expressed genes (DEGs) in patients with MI compared to normal controls with p value < 0.05 and |logFC| > 1. Furthermore, interaction network and sub-network of these of these DEGs were constructed by NetBox. Linker genes were screened in the Global Network database. The degree of linker genes were calculated by igraph package in R language. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis were performed for DEGs and network modules. A total of 246 DEGs were identified in MI, which were enriched in the immune response. In the interaction network, LCK, CD247, CD3D, FYN, HLA-DRA, IL2, CD8A CD3E, CD4, CD3G had high degree, among which CD3E, CD4, CD3G were DEGs while others were linker genes screened from Global Network database. Genes in the sub-network were also enriched in the immune response pathway. The genes with high degree may be biomarkers for MI diagnosis and therapy.
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