Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, adipocytes have been shown to be endocrine cells that secrete a variety of bioactive substances-the so-called adipocytokines. Among adipocytokines, tumor necrotizing factor alpha, plasminogen activator inhibitor 1, and heparin-binding epidermal growth factor-like growth factor are produced in adipocytes as well as already known organs, and they contribute to the development of vascular diseases. Visfatin is a very recently discovered visceral fat-specific protein that may be related to the development of obesity-related diseases such as diabetes mellitus and cardiovascular disease. In contrast to these adipocytokines, adiponectin, also a newfound adipose tissue-specific collagen-like protein, has been noted recently as an important antiatherogenic as well as antidiabetic protein. The function of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysfunction of adipocytes including oversecretion of tumor necrotizing factor alpha, plasminogen activator inhibitor 1, and heparin-binding epidermal growth factor-like growth factor, as well as hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, including adiponectin, is discussed with respect to atherosclerosis.
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PMID:Adipocytokines and metabolic syndrome. 1596 78

Adipose tissue, in addition to the storage of lipids function for lipids, plays active roles in normal metabolic homeostasis and in the development of several diseases, such as type 2 diabetes, dyslipaemia and atherosclerosis. These roles are mediated by adipocytokines, factors secreted by adipose tissue. These include tumor necrosis factors (TNF)-alpha, leptin, resistin, adiponectin or visfatin. Adipocytokines act in an autocrine, paracrine and endocrine manner. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of leptin, resistin or TNF-alpha in obesity, its level is negatively correlated with body mass index, and is decreased in presence of insulin resistance and in type 2 diabetes. Adiponectin may play a crucial role in the development of diabetes mellitus and high adiponectin levels should protect against impairment of glucose metabolism. Moreover, adipocytokines are involved in the pathogenesis of vascular diseases and may represent a link between obesity, diabetes, inflammation and atherosclerosis. Weight loss, exercise and some antidiabetic drugs also influence plasma adipocytokines levels. For instance, thiazolidinediones treatment in patients with type 2 diabetes resulted in an increased in plasma adiponectin levels and a decrease in circulating TNF-alpha concentrations.
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PMID:[Adipocytokines: link between obesity, type 2 diabetes and atherosclerosis]. 1603 96

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.
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PMID:Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come. 1631 Dec 15

Recent studies suggest that adipose tissue hormones ("adipokines") are involved in the pathogenesis of various complications of obesity, including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Apelin and visfatin are two recently described adipokines, although they are also synthesized outside adipose tissue. Apelin exists in at least three forms, consisting of 13, 17, or 36 amino acids, all originating from a common 77-amino-acid precursor. In the cardiovascular system, apelin elicits endothelium-dependent, nitric oxide-mediated vasorelaxation and reduces arterial blood pressure. In addition, apelin demonstrates potent and long-lasting positive inotropic activity which is preserved even in injured myocardium and is not accompanied by myocardial hypertrophy. Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia. In addition to regulating cardiovascular function, apelin inhibits water intake and vasopressin production. Visfatin, previously recognized as a pre-B cell colony-enhancing factor (PBEF), is abundantly expressed in visceral adipose tissue and is upregulated in some, but not all, animal models of obesity. Preliminary studies suggest that plasma visfatin concentration is also increased in humans with abdominal obesity and/or type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from insulin and exerts hypoglycemic effect by reducing glucose release from hepatocytes and stimulating glucose utilization in peripheral tissues. Thus, apelin and visfatin are unique among adipose tissue hormones in that they are upregulated in the obese state and both exert primarily beneficial effects.
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PMID:Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? 1694 Sep 39

Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the production of adiponectin, an anti-inflammatory adipokine, is reduced. This imbalanced production of pro- and anti-inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.
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PMID:The metabolic syndrome: metabolic changes with vascular consequences. 1718 62

Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
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PMID:Adipocytokines - novel link between inflammation and vascular function? 1722 78

Extending the productive lifespan of human cells could have major implications for diseases of aging, such as atherosclerosis. We identified a relationship between aging of human vascular smooth muscle cells (SMCs) and nicotinamide phosphoribosyltransferase (Nampt/PBEF/Visfatin), the rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of SMCs was preceded by a marked decline in the expression and activity of Nampt. Furthermore, reducing Nampt activity with the antagonist FK866 induced premature senescence in SMCs, assessed by serial quantification of the proportion of cells with senescence-associated beta-galactosidase activity. In contrast, introducing the Nampt gene into aging human SMCs delayed senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress. Nampt-mediated SMC lifespan extension was associated with increased activity of the NAD+-dependent longevity enzyme SIRT1 and was abrogated in Nampt-overexpressing cells transduced with a dominant-negative form of SIRT1 (H363Y). Nampt overexpression also reduced the fraction of p53 that was acetylated on lysine 382, a target of SIRT1, suppressed an age-related increase in p53 expression, and increased the rate of p53 degradation. Moreover, add-back of p53 with recombinant adenovirus blocked the anti-aging effects of Nampt. These data indicate that Nampt is a longevity protein that can add stress-resistant life to human SMCs by optimizing SIRT1-mediated p53 degradation.
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PMID:Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. 1730 30

Cardiovascular and metabolic risk depends not only on the overall obesity but also fat distribution is more powerfull predictor for risk factors. Adipose tissue produces and secretes a variety of bioactive peptides - adipokines The most recently described adipocyte secretory proteins contribute to the pathogenesis of impaired insulin secretion and insulin resistance, endothelial dysfunction, a proinflammatory state and promote progression of atherosclerosis. This review presents an overview of the adipose tissue secreted proteins (leptin, TNF-alpha, IL-6, adiponectin, resistin, visfatin, ASP, FIAF, MT) role and their regulation in the context of abdominal obesity and the adverse metabolic consequences.
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PMID:Metabolic effects associated with adipose tissue distribution. 1735 88

Visfatin is a newly identified adipocytokine that mimics insulin action. However, the pathophysiological role of visfatin in diabetic patients is not fully understood. The main purpose of this study was to investigate the association of plasma visfatin with endothelial function in patients with type 2 diabetes mellitus. In addition, the relationships of visfatin with oxidative stress, low-grade inflammation, atherosclerosis, adiponectin, plasma renin activity, and aldosterone were also explored, and the effect of pioglitazone on visfatin was examined. Visfatin levels were measured in 80 patients with type 2 diabetes mellitus and in 28 age-matched healthy subjects. Endothelial function was evaluated by using flow-mediated vasodilatation (FMD), oxidative stress was assessed by the level of urinary 8-iso-prostaglandin F2alpha, and atherosclerosis and inflammation were measured by using the intimal-medial complex thickness and the levels of high-sensitivity C-reactive protein and fibrinogen. Pioglitazone was administered for 12 weeks at a dose of 30 mg/d in a further 20 patients with type 2 diabetes mellitus. There was a significant negative correlation between the log10-transformed (log) plasma visfatin concentration and FMD or creatinine clearance (R=-0.2672, P=.0167; R=-0.2750, P=.0136). Log visfatin was also positively correlated with log urinary albumin excretion (R=0.2305, P=.0397). In addition, it was also found that visfatin had a significant negative correlation with plasma aldosterone (R=-0.2432, P=.0297). In stepwise regression analysis, creatinine clearance, log aldosterone, FMD, and sex showed a significant association with log visfatin (P=.0040, P=.0069, P=.0444, and P=.0487, respectively), and log 8-iso-prostaglandin F2alpha showed a tendency for an association (P=.0515). Pioglitazone therapy did not affect the visfatin concentration in the 20 pioglitazone-treated patients with diabetes, although a significant elevation of visfatin was obtained in a subgroup of 11 female patients (P=.0381). In conclusion, the current study showed that visfatin is negatively associated with vascular endothelial function evaluated by FMD and creatinine clearance, and positively associated with log urinary albumin excretion. Visfatin was also negatively correlated with circulating aldosterone. Pioglitazone therapy for 12 weeks did not affect the plasma visfatin concentration significantly in all diabetic patients, but a significant elevation in visfatin was obtained in women only.
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PMID:Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus. 1737

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1+/-2.1 versus 15.5+/-2.0 ng/ml, P=0.03). This effect correlated with baseline visfatin levels (r=0.51, P<0.01) and was independent of any lipid-lowering actions of rosuvastatin.
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PMID:Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia. 1793 20


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