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      In Patients with Coronary Artery Disease and Type 2 Diabetes, SIRT1 Expression in Circulating Mononuclear Cells Is Associated with Levels of Inflammatory Cytokines but Not with Coronary Lesions

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          Abstract

          While SIRT1 is significantly associated with atherosclerosis and diabetic complications, its relevance to coronary lesions in patients with coronary artery disease and type 2 diabetes has not been specifically investigated. Thus, we assessed SIRT1 expression in peripheral blood mononuclear cells in these patients. We found that SIRT1 expression did not significantly correlate with syntax scores from coronary angiography ( p > 0.05). Notably, plasma levels of the inflammatory cytokines tumor necrosis factor- α, monocyte chemoattractant protein-1, and high-sensitivity C-reactive protein were markedly higher in diabetic patients ( p < 0.05). In addition, SIRT1 expression was negatively correlated with levels of these cytokines, as well as that of interleukin-6 ( p < 0.05). In summary, the data indicate that SIRT1 expression in peripheral blood mononuclear cells is significantly correlated with inflammatory cytokines levels in patients with coronary artery disease and type 2 diabetes but not with the severity of coronary lesions.

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          Most cited references36

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          Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.

          Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.
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            The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease.

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              Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial.

              Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is controversial. To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007. Cardiac death or nonfatal myocardial infarction (MI). The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years. clinicaltrials.gov Identifier: NCT00769275.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2016
                31 March 2016
                : 2016
                : 8734827
                Affiliations
                1Department of Cardiovascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
                2Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
                Author notes

                Academic Editor: Ramazan Akdemir

                Article
                10.1155/2016/8734827
                4830703
                27123454
                4af42e67-e052-4834-a8ef-f909475b1178
                Copyright © 2016 Yuanmin Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 December 2015
                : 29 February 2016
                : 13 March 2016
                Categories
                Research Article

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