ABSTRACT
BACKGROUND: Myocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage response are recent research hotspots. Hence, we attempted to examine the role of C-X-C motif chemokine 16 (CXCL16) as a potential candidate in MI. METHODS: Human cardiomyocytes were treated with hypoxia/reoxygenation (H/R) to establish an in vitro cell model. GEO database provided the clinical data of MI patients and GSEA verified the relationship of chemokine and MI. CCK-8 and flow cytometry analyses were used to measure cell viability and apoptosis. Bioinformatics analysis and luciferase reporter assay were conducted to determine the correlation between CXCL16 and miR-545. qRT-PCR and western blot assays were performed to investigate the expression level of the indicated genes. The activity of lactate dehydrogenase (LDH) and the levels of TNF-α, IL-6, IL-1ß, and IL-10 were explored using ELISA assay. RESULTS: CXCL16 was increased in MI. CXCL16 knockdown can reverse the inhibitory effect of H/R treatment on cell viability, while overexpression of CXCL16 showed the opposite trend. MiR-545 directly targeted CXCL16 and negatively regulated CXCL16 levels. MiR-545 promoted cell proliferation and inhibited apoptosis in the MI cell model, which attenuated the CXCL16-induced injury on cardiomyocytes. CONCLUSION: These findings demonstrated that CXCL16 aggravated MI damage through being directly targeted by miR-545 and mediating inflammatory responses, thereby providing potential therapeutic targets for MI therapy.
Subject(s)
Chemokine CXCL16/genetics , MicroRNAs/genetics , Myocardial Infarction/genetics , Myocardium/metabolism , Apoptosis/genetics , Cell Hypoxia/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Chemokine CXCL16/antagonists & inhibitors , Flow Cytometry , Gene Knockdown Techniques , Humans , Inflammation/genetics , Inflammation/pathology , Inflammation/therapy , Myocardial Infarction/pathology , Myocardial Infarction/therapy , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Signal TransductionABSTRACT
Serum retinal binding protein 4 (RBP4) was recently described as a new liver- and adipocyte-derived signal that may contribute to Type 2 diabetes mellitus (T2DM) and insulin resistance. The aim of this study was to test whether the RBP4 gene could be used as a genetic marker to predict the development of T2DM amongst the Chinese population of Han. For this study, a normal control group of 115 healthy subjects and an experimental group of 107 patients with T2DM were examined. A combined method of denaturing high-performance liquid chromatography (DHPLC) and sequencing was applied to the detection of the RBP4 gene variants. Two SNPs, rs17484721 and rs36035572, were analyzed. Phenotypes and biochemical indicators related to the metabolism of glucose and lipid were measured. We found that there are significant differences between the control group and the patients group in terms of their respective distributions of genotype and allele frequency. The TG levels of the TT and II genotype was significantly higher than that of the TC + CC and ID + DD, respectively, in both patient group and control group. These findings suggest that the variations in the RBP4 gene may be associated with T2DM and serum triglyeride levels in the Han Chinese.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide , Retinol-Binding Proteins, Plasma/genetics , Adult , Base Sequence , Case-Control Studies , China , Chromatography, High Pressure Liquid/methods , DNA Mutational Analysis/methods , Diabetes Mellitus, Type 2/blood , Female , Gene Frequency , Genetic Linkage/physiology , Haplotypes , Humans , Male , Middle Aged , Molecular Sequence Data , Triglycerides/bloodABSTRACT
AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.
