Increased oxidative stress in vascular cells is implicated in the pathogenesis of atherosclerosis. Reactive oxygen species (ROS) induce vascular inflammation via the proinflammatory cytokine/NF-kappaB pathway. Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) is an important regulator of intracellular ROS levels. However, no studies have examined the effects of PGC-1alpha on this process. We investigated the effects of PGC-1alpha on inflammatory molecule expression and activity of the redox-sensitive transcription factor, NF-kappaB, in vascular cells. PGC-1alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid. Tumor necrosis factor-alpha (TNF-alpha), a major proinflammatory factor in the development of vascular inflammation, stimulates intracellular ROS production through an increase in both mitochondrial ROS and NAD(P)H oxidase activity. Adenovirus-mediated overexpression of the PGC-1alpha gene in HASMCs and HAECs leads to a significant reduction in intracellular and mitochondrial ROS production as well as NAD(P)H oxidase activity. Consequently, NF-kappaB activity and MCP-1 and VCAM-1 induced by TNF-alpha are suppressed. Our data support the possibility that agents stimulating PGC-1alpha expression in the vasculature aid in preventing the development of atherosclerosis.
Abbreviations: ALA, α-lipoic acid; AP-1, activator protein-1; MMP-9, matrix metalloproteinase-9; VSMC, vascular smooth muscle cell
AbstractThe migration of vascular smooth muscle cells (VSMCs) into the intima, an important step in injury-induced neointimal hyperplasia, requires the activation of nuclear factor-κB (NF-κB) and the consequent up-regulation of matrix metalloproteinase-9 (MMP-9). This study was undertaken to test for a possible effect of α-lipoic acid (ALA), a potent inhibitor of NF-κB, on MMP-9 expression. ALA inhibited high-glucose-and TNF-α-stimulated VSMC migrations in vitro. It also inhibited high-glucoseand TNF-α-induced increases in MMP-9 expression. The activity of MMP-9-promoter constructs with mutations in the NF-κB binding site was not inhibited by ALA, indicating an involvement of the NF-κB signaling pathway in the ALA-specific inhibition of MMP-9. These data suggest the possibility that ALA may be useful for the prevention of neointimal hyperplasia after angioplasty, by inhibiting the NF-κB/ MMP-9 pathway, especially with hyperglycemia.
The accurate diagnosis of heart failure in emergency room patients is quite important, but can also be quite difficult due to our insufficient understanding of the characteristics of heart failure. The purpose of this study is to design a decision-making model that provides critical factors and knowledge associated with congestive heart failure (CHF) using an approach that makes use of rough sets (RSs) and decision trees. Among 72 laboratory findings, it was determined that two subsets (RBC, EOS, Protein, O2SAT, Pro BNP) in an RS-based model, and one subset (Gender, MCHC, Direct bilirubin, and Pro BNP) in a logistic regression (LR)-based model were indispensable factors for differentiating CHF patients from those with dyspnea, and the risk factor Pro BNP was particularly so. To demonstrate the usefulness of the proposed model, we compared the discriminatory power of decision-making models that utilize RS- and LR-based decision models by conducting 10-fold cross-validation. The experimental results showed that the RS-based decision-making model (accuracy: 97.5%, sensitivity: 97.2%, specificity: 97.7%, positive predictive value: 97.2%, negative predictive value: 97.7%, and area under ROC curve: 97.5%) consistently outperformed the LR-based decision-making model (accuracy: 88.7%, sensitivity: 90.1%, specificity: 87.5%, positive predictive value: 85.3%, negative predictive value: 91.7%, and area under ROC curve: 88.8%). In addition, a pairwise comparison of the ROC curves of the two models showed a statistically significant difference (p<0.01; 95% CI: 2.63-14.6).
Radiofrequency catheter ablation of accessory pathways and the atrioventricular junction often requires multiple applications of energy. The inability to determine the effects of any given application on the underlying tissue may contribute to this problem. In the present study, impedance was monitored in 20 patients undergoing radiofrequency catheter ablation, and the relationship between an initial decrease in impedance and subsequent effects were examined. An initial fall in impedance of more than 10 omega was 78% sensitive and 88% specific for predicting subsequent evidence of tissue heating (interruption of conduction or an abrupt rise in impedance due to coagulum formation). In contrast, initial values of voltage, current, or impedance did not distinguish between effective and ineffective applications of radiofrequency energy. Continuous monitoring of impedance may facilitate radiofrequency catheter ablation.
Recent studies have suggested a favorable effect of cardiac rehabilitation (CR) on patients with cardiovascular disease. This study aimed to evaluate the impact of home-based exercise training with wireless monitoring on acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 55 ACS patients undergoing PCI were randomly divided into home based exercise training with wireless monitoring cardiac rehabilitation (CR, n = 26) and usual care (UC, n = 29). Exercise capacity and quality of life (QOL) were evaluated at baseline and after 12 weeks. Change of metabolic equivalent of the tasks, maximal exercise time and QOL were significantly increased (+2.47 vs +1.43, P = 0.021; +169.68 vs +88.31 sec, P = 0.012; and +4.81 vs +0.89, P = 0.022, respectively), and the change of submaximal rate pressure product, and of submaximal rate of perceived exertion were significantly decreased (-28.24 vs -16.21, P = 0.013; and -1.92 vs -1.62, P = 0.018, respectively) in the CR group compared to the UC group after 12 weeks. CR using home-based exercise training with wireless monitoring led to improvement of exercise capacity and QOL relative to conventional care in ACS patients undergoing PCI. Our findings suggest that early scheduled CR may be considered in ACS patients undergoing PCI.
BackgroundChemerin is a novel adipokine that is associated with inflammation and adipogenesis. However, it remains unclear whether chemerin is involved in patients with cardiovascular disease. We investigated whether the serum chemerin levels of Korean patients with coronary artery disease correlated with specific cardiometabolic parameters.MethodsIn total, 131 patients, all of whom had coronary artery stenosis exceeding 50%, participated in this study. Their serum chemerin levels and cardiometabolic parameters were measured. The serum chemerin levels of two groups of patients were compared; those with one stenotic vessel (n=68) and those with multiple stenotic vessels, including left main coronary artery disease (n=63).ResultsSerum chemerin levels correlated positively with the degree of coronary artery stenosis and fasting glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high sensitive C-reactive protein levels. The group with multiple stenotic vessels, including left main disease, had higher chemerin levels than the group with one stenotic vessel (t=-2.129, P=0.035). Multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease (odds ratio, 1.018; confidence interval, 0.997 to 1.040; P=0.091).ConclusionSerum chemerin levels have a significant correlation with several cardiometabolic risk factors and the degree of coronary artery stenosis in Korean patients with coronary artery disease. However, multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease. Additional investigations are necessary to fully elucidate the role of chemerin in cardiovascular disease.
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