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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular endothelium, building the inner layer of capillaries and blood vessels of all sorts, represents a highly active metabolic and endocrine organ producing a multitude of different molecules, including vasoactive peptide hormones, growth factors, coagulation factors and adhesion molecules. In addition, it expresses many of the respective endocrine, paracrine and cytokine/growth factor receptors. It thereby regulates the delicate balance between vasoconstriction and vasodilation, between coagulation and fibrinolysis, proliferation and apoptosis, as well as between transient adhesion and diapedesis of blood borne leukocytes. This minireview addresses the potential interactions of these important functions in the states of diabetes and of insulin resistance including obesity, hypertension and dyslipidaemia, all of which characterized by endothelial dysfunction.
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PMID:The endothelium as a metabolic and endocrine organ: its relation with insulin resistance. 1146 May 68

Targeted disruption of the klotho gene induces multiple phenotypes characteristic of human aging, including arteriosclerosis, pulmonary emphysema and osteoporosis. Moreover, we previously observed that insufficient klotho expression in mice leads to endothelial dysfunction. In the present study, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which exhibit hypertension, obesity, severe hyperglycemia and hypertriglyceridemia, and are thus considered an animal model of atherogenic disease, to test the effects of oral administration of troglitazone (200 mg/kg) on renal klotho mRNA expression and endothelial function. Systolic blood pressure, body weight, plasma glucose and triglyceride levels were all significantly higher in 30-week-old OLETF rats than in controls (LETO; Long-Evans Tokushima Otsuka) (p<0.05, n=7). In addition, endothelium-dependent relaxation of the aorta in response to 10(-5) M acetylcholine was significantly attenuated in OLETF rats (p<0.05, n=7), as was renal expression of klotho mRNA. Administration of troglitazone for 10 weeks significantly reduced systolic blood pressure, plasma glucose and triglyceride levels in OLETF rats, while augmenting endothelium-dependent aortic relaxation and renal klotho mRNA expression. These findings suggest that troglitazone protects the vascular endothelium against damage caused by the presence of multiple atherogenic factors.
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PMID:Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors. 1176 31

Over the past 10 years it has become clear that intact vascular function, especially at the level of the endothelium, is paramount in the prevention or delay of cardiovascular disease. It has also become clear that insulin itself, in addition to its metabolic actions, directly effects vascular endothelium and smooth muscle. Insulin, at normal physiologic concentrations, causes changes in skeletal muscle blood flow in healthy, insulin-sensitive subjects. Insulin's effect on the endothelium is mediated through its own receptor and insulin signalling pathways, resulting in the increased release of nitric oxide. Insulin's vascular actions are impaired in insulin-resistant conditions such as obesity, Type II (non-insulin-dependent) diabetes mellitus and hypertension, which could contribute to the excessive rates of cardiovascular disease in these groups. Insulin-resistant states of obesity and Type II diabetes show a multitude of metabolic abnormalities that could cause vascular dysfunction. Non-esterified fatty acid levels increase long before hyperglycaemia becomes present. Raised non-esterified fatty acids impair insulin's effect on glucose uptake in skeletal muscle and the vascular endothelium and thus could have detrimental effects on the vasculature, leading to premature cardiovascular disease.
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PMID:Vascular function, insulin resistance and fatty acids. 1262 32

Insulin resistance often clusters with other cardiovascular risk factors, such as obesity, impaired glucose tolerance (IGT), hypertension, dyslipidaemia and impaired fibrinolysis. Collectively, these endocrine and metabolic disturbances are described as the dysmetabolic syndrome, which is also commonly called the "insulin resistance syndrome", the "metabolic syndrome", or "syndrome X". Insulin resistance, working in concert with the other components of the dysmetabolic syndrome, induces deleterious changes to the vascular endothelium and lipid profiles that directly and indirectly promote the progression of atherosclerosis. Insulin resistance in adipocytes, leading to decreased suppression of lipolysis by insulin, may be especially important in this regard. Reduced suppression of lipolysis by insulin in obese subjects is associated with increased levels of fatty acids that damage the arterial wall and promote atherosclerosis. The lipid profiles of insulin-resistant subjects are often characterised by the appearance of hypertriglyceridaemia and small, dense LDL-cholesterol, together with low HDL-cholesterol. In addition, adipocytes are highly active endocrine organs and secrete a range of substances that reduce insulin sensitivity further. The net result of these derangements is a vicious circle, wherein the development of insulin resistance is strongly associated with atherogenic lipid profiles and endothelial dysfunction which, in turn, exacerbates insulin resistance. The consequences for the individual with dysmetabolic syndrome include an increased risk of cardiovascular disease of up to 4-fold compared with subjects without the dysmetabolic syndrome.
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PMID:The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. 1450 97

Disturbances of lipids metabolism described in obese persons are important factor damaging vascular endothelium. Known markers of endothelium impairment are: von Willebrand factor (vWf), tissue plasminogen activator (t-PA:Ag) and thrombomodulin (TM). The aim of the work was to evaluate markers of the endothelial disturbance in the blood plasma of persons with obesity. The study was performed in the group of 50 obese persons (39 W, 11 M) aged 35-65 (means 48.8) years with abdominal obesity. The control group consisted of 30 healthy volunteers aged 25-56 (means 41.0) years. In the poor platelet plasma obtained from venous citric blood concentrations of TM, von Willebrand factor antigen (vWf:Ag) and tissue plasminogen activator antigen (t-PA:Ag) were determined using immunoenzyme-linked assay (ELISA). In the obese persons significantly higher concentration of vWf:Ag and t-PA:Ag in comparison to control group. Analysis of results obtained according sex showed that in the blood plasma of obese women TM concentration was significantly higher than in healthy women. Our study proved that in the blood plasma of obese men there are evidences of impairment of endothelial function as higher concentration of vWf:Ag and t-PA:Ag, but in the group of obese women as the increased TM concentration.
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PMID:[Thrombomodulin, von Willebrand factor and tissue plasminogen activator in the blood plasma of obese women and men]. 1505 51

Two syndromes are called syndromes X: cardiac (effort anginal pain, positive exercise tolerance test and absence of angiographically documented critical stenosis in coronary arteries) and metabolic (according to WHO definition: impaired glucose tolerance and insulin resistance and > or = 2 risk factors from the following list: hypertension, dyslipidaemia, visceral obesity and microalbuminuria). Hyperinsulinaemia and endothelial dysfunction are present in both syndromes. The contribution of endothelial nitric oxide synthase gene mutations to the etiology of these syndromes is also studied. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of nitric oxide (NO), enhanced inactivation of NO after its release from endothelial cells or enhanced synthesis of vasoconstricting agents. It has been demonstrated that insulin exerts a direct hypertrophic effect on the vascular endothelium and the smooth muscle cells. The hemodynamic properties of insulin have also been discussed. Some findings suggest that in the skeletal muscle circulation, insulin stimulates both endothelin-1 (ET-1) and nitric oxide activity and an imbalance between the release of these two substances may be involved in the pathophysiology of endothelial dysfunction.
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PMID:[Do syndromes X, cardiac and metabolic, have any similar characteristics?]. 1523 88

Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability. Therefore altered insulin signalling in the endothelium represents a candidate mechanism underlying the association between insulin resistance and endothelial dysfunction. In recent years, it has become apparent that insulin sensitivity is regulated by the adipocytokines, a group of bioactive proteins secreted by adipose tissue. Secretion of adipocytokines is altered in obese individuals and there is increasing evidence that the adipocytokines have direct effects on the vascular endothelium. A number of current antidiabetic strategies have been demonstrated to have beneficial effects on endothelial function and to alter adipocytokine concentrations in addition to their effects on glucose homoeostasis. In this review we will explore the notion that the association between insulin resistance and endothelial dysfunction is accounted for by adipocytokine action on the endothelium. In addition, we examine the effects of weight loss, exercise and antidiabetic drugs on adipocytokine availability and endothelial function.
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PMID:The role of insulin and the adipocytokines in regulation of vascular endothelial function. 1532 98

Endothelial release of tissue-type plasminogen activator (t-PA) regulates fibrinolysis and is considered to be a primary endogenous defense mechanism against thrombosis. Adiposity is associated with an increased risk of atherothrombotic events. We determined the influence of overweight and obesity on the capacity of the vascular endothelium to release t-PA and the effects of regular aerobic exercise on endothelial t-PA release in previously sedentary overweight and obese adults. First, we studied 66 sedentary adults: 28 normal-weight (BMI < 25 kg/m2); 22 overweight (BMI > or = 25 and < 30 kg/m2); and 16 obese (BMI > or = 30 kg/m2). Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin (BK) and sodium nitroprusside. Second, we studied 17 overweight and obese adults who completed a 3-mo aerobic exercise intervention. Net release of t-PA in response to BK was approximately 45% lower (P < 0.01) in overweight (from 0.1 +/- 0.4 to 41.7 +/- 4.9 ng x 100 ml tissue(-1) x min(-1)) and obese (-0.1 +/- 0.6 to 47.7 +/- 5.2 ng x 100 ml tissue(-1) x min(-1)) compared with normal-weight (0.1 +/- 0.8 to 77.5 +/- 6.7 ng x 100 ml tissue(-1) x min(-1)) adults. There was no difference in t-PA release between the overweight and obese groups. Exercise training significantly increased t-PA release capacity in overweight and obese adults (from -0.3 +/- 0.5 to 37.1 +/- 4.9 ng x 100 ml tissue(-1) x min(-1) before training vs. 1.0 +/- 0.9 to 65.4 +/- 6.3 ng x 100 ml tissue(-1) x min(-1) after training) to levels comparable with those of their normal-weight peers. These results indicate that overweight and obesity are associated with profound endothelial fibrinolytic dysfunction. Importantly, however, regular aerobic exercise can increase the capacity of the endothelium to release t-PA in this at-risk population.
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PMID:Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise. 1598 56

Leptin is an adipocyte-derived hormone that plays a major role in the regulation of energy homeostasis through its action in the central nervous system. Leptin also acts on several peripheral tissues, including the vascular endothelium. The leptin receptor has been identified in endothelial cells. Leptin action on the endothelium modulates several physiologic processes, with potential implications in pathophysiologic diseases associated with obesity. Leptin stimulation of angiogenesis has attracted attention because of its potential involvement in retinopathy and atherosclerosis. Leptin activation of endothelial oxidative stress also has implications in atherosclerosis and inflammation. However, data on the impact of the endothelial effect of leptin on arterial pressure are contrasting. Although some investigators have shown that leptin action on the endothelial nitric oxide system tends to decrease arterial pressure, others have shown no contribution from the endothelial effect of leptin to the control of arterial pressure. Further characterization of the endothelial effects of leptin will, it is hoped, help in the understanding of the different pathophysiologic diseases associated with obesity.
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PMID:Endothelial effects of leptin: implications in health and diseases. 1603 75

Cardiovascular disease is the leading cause of death among dialysis patients. The relative risk of mortality increases as serum albumin concentration and body mass index decline. While these are generally associated with nutritional status, inflammation causes sarcopenia and decreased albumin concentration by reducing synthesis of proteins and increasing their catabolic rate. While inflammation can arise from atherosclerotic blood vessels, systemic inflammation from any source can alter the vascular endothelium and plasma protein composition in ways that promotes vascular injury. High-density lipoprotein synthesis is decreased and the high-density lipoprotein present is less capable of reducing inflammation. Activation of neutrophils favors lipoprotein oxidation. Surprisingly, while obesity is associated with cytokine production in patients without renal failure, as well as among dialysis patients, increased body mass index, whether reflecting muscle mass or adipose tissue, is associated with a decline in mortality rates.
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PMID:Association between inflammation and malnutrition as risk factors of cardiovascular disease. 1636 41


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