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  • br AGE effects in CAD pathophysiology Recent


    AGE effects in CAD pathophysiology Recent studies demonstrate an association between increased AGE levels and the incident of cardiovascular events in diabetic patients being implicated in increased arterial wall stiffness, arrhythmias, systolic and diastolic dysfunction, congestive heart failure, coronary artery diseases and in-stent restenosis risk [2]. In EPIC-NL cohort study with a large number of type 2 diabetic patients, high plasma protein-bound CML, CEL and pentosidine levels were found to significantly correlate with high risk incident of cardiovascular disease after adjustment for confounding factors [16]. In accordance, recent studies demonstrate that elevated plasma levels of methylglyoxal hydroimidazolone, MGH1, CML, CEL, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and low levels of two oxidation products (2-aminoadipic Sevoflurane and methionine sulfoxide) were associated with the severity of coronary atherosclerosis and incident of cardiovascular events in patients with T2D [17,18]. Importantly, previous studies on patients undergoing coronary angiography have shown a correlation of elevated serum AGEs in patients with normal glucose and 3-vessel disease compared to no-obstructive disease [19]. Additionally, elevated pentosidine levels were correlated with CAD severity in patients with obstructive CAD, independent of diabetic status [20].
    Therapeutic targeting of ages for CAD
    Conclusion AGEs constitute a critical family of molecules with pivotal role in the pathophysiology of coronary heart disease [1,2]. Being directly implicated in vascular stiffness and atherosclerosis as well as in modulation of intracellular signaling with detrimental effects in endothelial cell response, VSMCs function and platelet activity, AGEs should be considered as major cardiometabolic risk factors [3]. In addition, their interference with the available treatment modalities predisposes individuals to a persistent cardiovascular risk, emphasizing the need to improve their analytical measurement, establish their biomarker potential [16] and integrate them in risk stratification of patients as well as in treatment decisions. Future studies should also focus on detection of protein bound high molecular weight AGEs commonly present in exogenous sources and characterize their potential toxic effects in vascular tissue [8,21]. The synergistic action of dietary AGEs to endogenous load further indicates the need for lifestyle changes in preventive and therapeutic schemes of myocardial ischemia and its complications [3,15,81,98,99], along with selective AGE/RAGE modulating drugs [100].
    Conflict of interest
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    Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome [1]. Current treatment of NAFLD is based on weight reduction [2]. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities [3,4]. Bariatric surgery has beneficial effects not only in weight loss, but also in the metabolic alterations encompassed by the metabolic syndrome [5,6]. In addition, insulin resistance, lipid profile, inflammation, and adipokines which involved in the development of NAFLD have been changed favorably after bariatric surgery [7]. Roux-en-Y Gastric Bypass (RYGB) is a popular and efficacious form of bariatric operation, which remains one of the most effective options in treatment of NAFLD [[8], [9], [10]]. Although great efforts have been dedicated to elucidate the underlying mechanisms involved in amelioration of fatty liver, the mechanisms are still needed to be further explored. Up-regulated hepatic AMP-activated protein kinase (AMPK) plays a critical role in the resolution of steatosis after RYGB [11]. AMPK regulates lipid and glucose metabolism through direct phosphorylation of its substrates and indirect control over gene transcription [12]. Mechanistic target-of-rapamycin (mTOR) is one of the key downstream targets of AMPK [13]. mTOR protein is a serine-threonine kinase belonging to the phosphoinositide 3-kinase (PI3K)-related kinase family that plays key roles in lipid biosynthesis [[14], [15], [16]]. mTOR has been shown to activate the transcription factor, SREBP, which in turn activates ACC, FAS, and stearoyl-coenzyme A desaturase (SCD) enzymes involved in lipogenesis [[17], [18], [19]]. Although the exact mechanism by which SREBP1 and SREBP2 are regulated by mTOR is unclear, it is believed to be mediated by S6K1 [17,18]. The transcriptional regulation of SREBP1c by insulin is not dependent on S6K, whereas post-transcriptional processing of SREBP1c is S6K dependent [20].