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Background: Recent studies suggest that classical coronary risk factors play a significant role in the pathogenesis of coronary artery disease. Our study aims to explore the interaction of circRNA with classical coronary risk factors in coronary atherosclerotic disease. Method: Combined analysis of RNA sequencing results from coronary segments and peripheral blood mononuclear cells of patients with coronary atherosclerotic disease was employed to identify critical circRNAs. Competing endogenous RNA networks were constructed by miRanda-3.3a and TargetScan7.0. The relative expression quantity of circRNA in peripheral blood mononuclear cells was determined by qRT-PCR in a large cohort including 256 patients and 49 controls. Spearman's correlation test, receiver operating characteristic curve analysis, multivariable logistic regression analysis, one-way analysis of variance, and crossover analysis were performed. Results: A total of 34 circRNAs were entered into our study, hsa_circRPRD1A, hsa_circHERPUD2, hsa_circLMBR1, and hsa_circDHTKD1 were selected for further investigation. A circRNA-miRNA-mRNA network is composed of 20 microRNAs and 66 mRNAs. The expression of hsa_circRPRD1A (P = 0.004) and hsa_circHERPUD2 (P = 0.003) were significantly down-regulated in patients with coronary artery disease compared to controls. The area under the curve of hsa_circRPRD1A and hsa_circHERPUD2 is 0.689 and 0.662, respectively. Univariate and multivariable logistic regression analyses identified hsa_circRPRD1A (OR = 0.613, 95%CI:0.380–0.987, P = 0.044) as a protective factor for coronary artery disease. Based on the additive model, crossover analysis demonstrated that there was an antagonistic interaction between the expression of hsa_circHERPUD2 and alcohol consumption in subjects with coronary artery disease. Conclusion: Our findings imply that hsa_circRPRD1A and hsa_circHERPUD2 could be used as biomarkers for the diagnosis of coronary artery disease and provide epidemiological support for the interactions between circRNAs and classical coronary risk factors. [ABSTRACT FROM AUTHOR]

Background: Complications of diabetes mellitus (DM) are related not only to elevated plasma glucose, but also plasma glucose fluctuations. However, the specific mechanism underlying the role of plasma glucose fluctuation in the pathogenesis of DM complications remains poorly understood. In the present study, the influence of acute fluctuant hyperglycemia and persistent hyperglycemia on vascular endothelial cell apoptosis, function, oxidative stress and inflammation was examined in vivo., Methods: Rats were assigned to three different groups (n = 10/group) that received 48-h infusions of saline (SAL group), continuous 50 % glucose (constant high glucose group [CHG]), or intermittent 50 % glucose (acute blood glucose fluctuation group [AFG]). Plasma 8-isoprostaglandin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were quantified by using enzyme-linked immunosorbent assay (ELISA) commercial kits. Plasma insulin levels were measured by radioimmunoassays (RIAs) using kits. The aortic segment was collected. The levels of malondialdehyde (MDA) and activity of glutathione peroxidase (GSH-PX) were measured in endothelial homogenates prepared from endothelial cells harvested from the aorta using colorimetric kits. Apoptosis of vascular endothelial cells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Endothelial dysfunction was assessed by isometric tension recording to evaluate the endothelial function. The expression of B cell lymphoma-2 (Bcl-2), Bcl-2 Associated X protein (Bax), pro caspase-3, caspase-3 p17, 3-nitrotyrosine (3-NT) and p47phox protein in rat aortic endothelial cells were tested with Western blot analysis. Endothelial cells reactive oxygen species (ROS) formation was determined using dihydroethidium-dependent fluorescence microtopography in aortic cryo-sections. Expression of IL-6, TNF-α and ICAM-1 mRNAs in vascular endothelial cells were determined by real-time quantitative PCR., Results: Endothelial cells apoptosis and dysfunction were observed significantly in the aortas of the AFG group (P < 0.05). The AFG had reduced Bcl-2 and pro caspase-3 levels and enhanced Bax mitochondrial translocation and caspase-3 p17 protein levels in comparison with the CHG group (P < 0.05). Both AFG and CHG induced β-cell dysfunction and insulin resistance (P < 0.05). AFG increased MDA and 8-isoprostaglandin levels in plasma, oxidative stress in vascular endothelial cells, and inflammatory cytokines in plasma and vascular endothelial cells (P < 0.05)., Conclusion: Acute glucose fluctuation may cause significant oxidative stress and inflammation in endothelial cells, increase the adhesion of monocytes to endothelial cells, and elevate endothelial cell apoptosis, resulting in severe cardiovascular injury.