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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin and resistin are proteins that affect insulin resistance and atherosclerosis significantly. We investigated adiponectin and resistin concentrations as predictors of cardiovascular events in Korean patients with type 2 diabetes. The study in 2001 comprised 343 unrelated patients with type 2 diabetes (65+/-9.2 years old). They were followed up for 42 months. The baseline duration of diabetes, smoking status and history of cardiovascular diseases (CVD) were recorded. BMI, blood pressures, HbA1c, lipid profiles, ECG, creatinine and urine microalbumin were measured. Adiponectin and resistin were measured using enzyme-linked immunosorbent assays. The primary endpoint was defined as one of cardiovascular death, myocardial infarct, CABG, stroke, unstable angina or overt nephropathy. Thirty-eight patients (11.1%) experienced primary endpoint during the follow-up. After adjustment for age, sex, BMI, blood pressure and lipid status, participants in the lowest quartile of adiponectin levels compared with the highest had significantly increased risk of primary endpoint (relative risk=3.03; 95% CI 1.09-8.41; p=0.034). In contrast, resistin level had no influence on the risk of primary endpoint. A low level of adiponectin, not resistin, was a significant risk factor for the development of cardiovascular events in these Korean patients with type 2 diabetes.
Atherosclerosis 2008 Jan
PMID:Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month prospective study. 1717 23

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

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

Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors, similar to overt Cushing syndrome. Data about the involvement of the adipokines in the development of insulin resistance and atherosclerosis in AI are completely lacking. The aim of the present study was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5 +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5 males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8 kg/m(2)) with AI and typical computed tomographic features of cortical adenoma, who were not affected by diabetes mellitus, hypertension, or other relevant diseases. All patients underwent anthropometric measurements and determination of basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight dexamethasone test and 250-microg corticotropin test were performed in all cases. A subclinical Cushing syndrome was found in 3 patients, whereas the others had apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/- 0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2 ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5 pg/mL, respectively; P < .05) and apparently not affected by the presence of visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P < .01). In conclusion, patients with AI may show increased levels of adipokines (apparently not related to the presence of diabetes, hypertension, or obesity), which may be affected by the presence of the adrenal adenoma. For some adipokines, a direct production from the adrenal gland may be hypothesized even if other studies are needed to better investigate the role of adipokines in states of altered cortisol secretion.
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PMID:Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. 1744 45

It is estimated that 60%-7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.
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PMID:Cardiometabolic aspects of polycystic ovarian syndrome. 1758 75

Adipocyte cytokines regulate glucose metabolism and insulin resistance and adiponectin is thought to have a protective effect against atherosclerosis. Studies have shown that adiponectin expression is decreased in obese subjects and those with metabolic syndrome or diabetes mellitus. The purpose of this study was to investigate the relationship between circulating adipocyte cytokine concentrations and angiographic coronary artery disease (CAD) progression in patients with chest pain. Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization between March 1999 and January 2004 were enrolled. A modified Gensini scoring system was used to define angiographic coronary artery progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary lesions were classified into the progression group (N=55). Those who did not have CAD progression were classified into the non-progression group (N=102). Univariate analysis showed that CAD progression was associated with male gender (93% vs. 78%, p=0.038), higher baseline total cholesterol (187+/-43 vs. 173+/-39 mg/dl, p=0.037) and higher baseline fasting blood glucose (128+/-57 vs. 110+/-40 mg/dl, p=0.037). Patients in the progression group had a significantly lower serum adiponectin level (14.3+/-7.9 vs. 18.9+/-13.2 mug/ml, p=0.007) than, but resistin (28.9+/-13.4 vs. 34.4+/-26.0 ng/ml, p=0.142) and leptin (7.4+/-4.6 vs. 7.7+/-6.5 ng/ml, p=0.675) levels similar to, those in the non-progression group. In a multivariate binary logistic regression model, male gender (odds ratio 4.283, p=0.015), higher serum cholesterol (odds ratio 1.010, p=0.032) and lower serum adiponectin (odds ratio 0.959, p=0.030) were all significant independent predictors of CAD progression. In conclusion, we found that a decreased circulating level of adiponectin is associated with angiographic CAD progression in patients with angina pectoris.
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PMID:Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. 1917 15

Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) are strongly associated with levels of low-density lipoprotein cholesterol in the blood plasma and, thereby, occurrence or resistance to atherosclerosis and coronary heart disease. Despite this importance, relatively little is known about the biology of PCSK9. Here, the crystal structure of a full-length construct of PCSK9 solved to 1.9-A resolution is presented. The structure contains a fully folded C-terminal cysteine-rich domain (CRD), showing a distinct structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules. This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD.
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PMID:The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain. 1780 97

Obesity is a highly prevalent disease with multiple implications for cardiovascular morbidity and mortality. The traditional view of obesity is that excessive adipose tissue represents a passive storage depot of excess energy. However, obesity has been demonstrated to be a highly active endocrine organ with multiple metabolic pathways that interact with classic cardiac risk factors. The role of inflammation in atherosclerosis has been clarified by the ready availability of a variety of markers, including C-reactive protein, adiponectin, tumor necrosis factor-alpha, hemostatic markers, resistin, and a variety of emerging markers such as interleukins and adhesion molecules. Adipose tissue has been demonstrated to be the site of synthesis of a variety of proteins that are intimately involved in the regulation of inflammation. The concept that obesity represents an inflammatory state has gained credence over the past decade and has provided insights into the mechanisms of atherosclerosis and risk factor interaction.
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PMID:Obesity and inflammation: a new look at an old problem. 1787 22

The prevalence of obesity is rising dramatically in developed and developing countries. Obesity contributes to increased mortality from numerous causes, but the most important of these is cardiovascular death. The relationship between obesity and atherogenesis is multifactorial, including alterations in the composition and level of lipoproteins, changes in blood pressure, and changes in circulating coagulation and inflammatory factors. Mouse models can be useful for dissecting selected aspects of this complex relationship. One area in which these models can be of particular value is in investigating the effect of secretory products of adipose tissue on the vessel wall. Adipocytes and adipose tissue secrete numerous factors and their level of expression is altered in obese states. Adipose tissue and adipocytes produce adiponectin, resistin, leptin, and apolipoproteins (serum amyloid A and apoE); all of which can directly impact vessel wall homeostasis. Mouse models utilizing deletion or overexpression of many of these factors have demonstrated an important impact of these on vessel wall homeostasis. Subsequent to the development of obesity, factors secreted from adipose tissue have also been shown to have direct effect on liver production of systemic inflammatory factors. Mouse models have validated the importance of angiotensin II, TNFalpha, and MCP-1 for impacting vessel wall health in obese states. In summary, excess adipose tissue produces myriad changes in organismal homeostasis with potential impact on the vessel wall. The power of mouse genetics permits targeted mechanistic investigation for understanding how obesity accelerates atherosclerosis in a complex in vivo milieu.
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PMID:Adipose tissue and the vessel wall. 1804 97


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