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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
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PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Studies of diabetic vascular disease have traditionally used murine models of type 1 diabetes and genetic models of type 2 diabetes. Because the majority of patients with type 2 diabetes have diet induced obesity, we sought to study the effect of diabetes on arterial disease in a mouse model of diet induced obesity/diabetes. C57Bl/6 mice fed a high-fat diet for 9 weeks developed type 2 diabetes characterized by elevated body weight, hyperglycemia, and hyperinsulinemia. Arteries from diabetic mice exhibited a marked decrease in endothelium-dependent vasodilation, a modest decrease in endothelium independent vasodilation, and an increase in sensitivity to adrenergic vasoconstricting agents. Insulin stimulated protein kinase B (akt) and endothelial nitric oxide synthase (eNOS) phosphorylation were preserved in arteries from diabetic mice; however, eNOS protein dimers were markedly diminished. Arterial nitrotyrosine staining indicated that increased levels of peroxynitrite contributed to eNOS dimer disruption in the diabetic mice. The abnormal vasomotion was not an acute response to the high-fat diet, as short term high-fat diet feeding had no effect on endothelium dependent dilation. A trend toward smaller neointimal lesions was noted in high-fat diet fed mice after femoral artery wire denudation injury. In summary, disrupted eNOS dimer formation rather than impaired insulin mediated eNOS phosphorylation contributed to the endothelial dysfunction in diet induced obese/diabetic mice. The lack of an increase in neointimal formation indicates that additional diabetes associated parameters (such as hyperlipidemia and atherosclerotic vascular disease) may need to be present to increase neointimal formation in this model.
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PMID:Diabetes induces endothelial dysfunction but does not increase neointimal formation in high-fat diet fed C57BL/6J mice. 1610 22

Hypertension and cardiovascular disease are leading causes of morbidity and mortality. Accumulating data demonstrate a relationship between hypertension and several vascular and metabolic abnormalities that are components of the cardiometabolic syndrome. The components of the cardiometabolic syndrome include insulin resistance/hyperinsulinemia, central obesity, dyslipidemia, hypertension, microalbuminuria, increased inflammation, and oxidative stress. There is growing evidence that tissue activation of the renin-angiotensin-aldosterone system participates in endothelial dysfunction, microalbuminuria, insulin resistance, and subsequent cardiovascular and chronic kidney disease. The notion that hypertension is a metabolic as well as a vascular disease opens a new paradigm for the treatment of this disorder.
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PMID:Hypertension and the cardiometabolic syndrome. 1610 58

Accelerated atherosclerosis is one of the major vascular complications of diabetes. Factors including hyperglycemia and hyperinsulinemia may contribute to accelerated vascular disease. Among the several mechanisms proposed to explain the link between hyperglycemia and vascular dysfunction is the hexosamine pathway, where glucose is converted to glucosamine. Although some animal experiments suggest that glucosamine may mediate insulin resistance, it is not clear whether glucosamine is the mediator of vascular complications associated with hyperglycemia. Several processes may contribute to diabetic atherosclerosis including decreased vascular heparin sulfate proteoglycans (HSPG), increased endothelial permeability and increased smooth muscle cell (SMC) proliferation. In this study, we determined the effects of glucose and glucosamine on endothelial cells and SMCs in vitro and on atherosclerosis in apoE null mice. Incubation of endothelial cells with glucosamine, but not glucose, significantly increased matrix HSPG (perlecan) containing heparin-like sequences. Increased HSPG in endothelial cells was associated with decreased protein transport across endothelial cell monolayers and decreased monocyte binding to subendothelial matrix. Glucose increased SMC proliferation, whereas glucosamine significantly inhibited SMC growth. The antiproliferative effect of glucosamine was mediated via induction of perlecan HSPG. We tested if glucosamine affects atherosclerosis development in apoE-null mice. Glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects.
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PMID:Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: evidence for a protective role for glucosamine in atherosclerosis. 1620 78

Diabetes mellitus with its increasing prevalence is a major global health problem in United States. Macrovascular complications, especially atherosclerosis, are the major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Metabolic syndrome is considered to be a metabolic precursor of type 2 diabetes mellitus and is an independent risk factor in the pathogenesis of atherosclerosis. It is a constellation of proatherogenic metabolic abnormalities, which include obesity, hypertension, characteristic dyslipidemia, hyperglycemia, insulin resistance, and compensatory hyperinsulinemia. Recent epidemiological data have demonstrated a strong causal association between insulin resistance and coronary vascular disease independent of hyperglycemia associated with type 2 diabetes mellitus. Given the high prevalence of metabolic syndrome in the general population and its role in the pathogenesis of atherosclerosis, every attempt should be made to recognize early the metabolic syndrome and to modify the associated proatherogenic metabolic abnormalities. Management of atherosclerosis in insulin-resistant states like metabolic syndrome and type 2 diabetes is a multifactorial process involving nonpharmacological interventions like exercise, diet control, and pharmacological therapy directed at hypertension, hyperglycemia, and dyslipidemia. Further research is warranted to demonstrate the effects of these interventions unequivocally in preventing the progression of metabolic syndrome to overt type 2 diabetes mellitus with its associated macrovascular complications.
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PMID:Managing atherosclerosis in patients with type 2 diabetes mellitus and metabolic syndrome. 1642 24

Fibrates, activators of the nuclear receptor PPARalpha, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARalpha activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. Eighteen normal-weight subjects were studied in four stages: at baseline, after 21 days of fenofibrate (160 mg/day) alone, after 3 days of dexamethasone (8 mg/day) added to fenofibrate, and after 3 days of dexamethasone added to placebo (dexamethasone alone). Dexamethasone alone caused hyperinsulinemia, increased glucose, decreased glucose disposal, and reduced insulin-induced suppression of hepatic glucose production as determined by hyperinsulinemic euglycemic clamp and increased systolic blood pressure as determined by ambulatory monitoring, features associated with an insulin-resistant state. Fenofibrate improved fasting LDL and total cholesterol in the setting of dexamethasone treatment but had no significant effect on levels of insulin or glucose, insulin-stimulated glucose disposal, or insulin suppression of glucose production during clamps, or ambulatory monitored blood pressure. In the absence of dexamethasone, fenofibrate lowered fasting triglycerides and cholesterol but unexpectedly increased systolic blood pressure by ambulatory monitoring. These data suggest that PPARalpha activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure.
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PMID:PPARalpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans. 1686 25

In patients with type II diabetes mellitus, the prevalence of hypertension is increased as much as twofold over that in the nondiabetic population. Hypertension in diabetic patients increases the risk and accelerates the course of development of cardiac disease, stroke, peripheral vascular disease, retinopathy, and nephropathy. Despite the importance of hypertension in type II diabetics, the basic mechanisms that initiate and sustain hypertension in these patients are poorly understood. Contributing factors discussed in this review include the following: obesity, insulin resistance, hyperinsulinemia, genetic factors, and abnormalities of cellular cation homeostasis. Also discussed are the features of hypertension in type II diabetic individuals which are reminiscent of the hemodynamic abnormalities characterizing hypertension in the elderly, including increased vascular reactivity and increased atherosclerotic vascular disease. Recent evidence has shown that insulin resistance and hyperinsulinemia exist in as many as 50 to 70% of adult nonobese individuals with untreated hypertension. These observations strongly suggest that the disease known as hypertension is characterized by fundamental abnormalities of metabolism as well as by hemodynamic alterations. This review discusses the mechanisms by which hyperinsulinemia and/or insulin resistance may lead to hypertension. Elevated levels of triglycerides in plasma and suppressed high-density lipoprotein cholesterol concentrations are often observed in hypertensive individuals. These elevations may result, in part, from hyperinsulinemia and/or insulin resistance. Information will be presented suggesting that subtle abnormalities of carbohydrate metabolism that exist in patients with hypertension may contribute to the accelerated cardiovascular disease that accompanies the hypertension state. This review also addresses both special concerns about metabolic consequences of antihypertensive therapy in hypertensive patients with subtle carbohydrate intolerance as well as those in hypertensive patients with overt diabetes.
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PMID:Relationship between hypertension and subtle and overt abnormalities of carbohydrate metabolism. 1698 76

Polycystic ovary syndrome (PCOS) is a complex disorder comprising both hormonal and metabolic abnormalities that include impaired glucose tolerance, type 2 diabetes, vascular disease, dyslipidemia, and obstructive sleep apnea. Insulin resistance is a central pathogenetic factor in PCOS that seems to result from a post-receptor-binding defect in insulin action. Insulin resistance and the consequent development of hyperinsulinemia contribute to the constellation of cardiometabolic abnormalities noted above. Although there is a paucity of data in regard to cardiovascular event rates and mortality in PCOS, an increased prevalence of cardiovascular risk factors has been well documented. Attention to the metabolic risks associated with PCOS, starting as early as adolescence, is essential to the medical care of these patients.
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PMID:Cardiometabolic features of polycystic ovary syndrome. 1825 Jun 36

The bidirectional interaction between coagulation and inflammation, which is relevant in various disease states that are dominated by systemic inflammatory responses, such as severe infection or chronic vascular disease, is modulated by metabolic factors. Changes in lipoprotein metabolism affect the inflammation-induced activation of coagulation, which may have impact on downstream effects, including organ dysfunction and survival. Likewise, glucose and insulin seem to influence inflammation-induced effects on coagulation and fibrinolysis. Hyperglycemia affects inflammation-induced and tissue factor-driven activation of coagulation, whereas hyperinsulinemia modulates the fibrinolytic response. There are indications that this modulatory role of metabolic factors in inflammation and coagulation may also have an impact on clinical outcome in various disease states.
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PMID:Metabolic modulation of inflammation-induced activation of coagulation. 1839 40

Hyperinsulinemia plays a major role in the pathogenesis of vascular disease. Restenosis occurs at an accelerated rate in hyperinsulinemia and is dependent on increased vascular smooth muscle cell movement from media to neointima. PDGF plays a critical role in mediating neointima formation in models of vascular injury. We have reported that PDGF increases the levels of protein tyrosine phosphatase PTP1B and that PTP1B suppresses PDGF-induced motility in cultured cells and that it attenuates neointima formation in injured carotid arteries. Others have reported that insulin enhances the mitogenic and motogenic effects of PDGF in cultured smooth muscle cells and that hyperinsulinemia promotes vascular remodeling. In the present study, we tested the hypothesis that insulin amplifies PDGF-induced cell motility by suppressing the expression and function of PTP1B. We found that chronic but not acute treatment of cells with insulin enhances PDGF-induced motility in differentiated cultured primary rat aortic smooth muscle cells and that it suppresses PDGF-induced upregulation of PTP1B protein. Moreover, insulin suppresses PDGF-induced upregulation of PTP1B mRNA levels, PTP1B enzyme activity, and binding of PTP1B to the PDGF receptor-beta, and it enhances PDGF-induced PDGF receptor phosphotyrosylation. Treatment with insulin induces time-dependent upregulation of phosphatidylinositol 3-kinase (PI3-kinase)-delta and activation of Akt, an enzyme downstream of PI3-kinase. Finally, inhibition of PI3-kinase activity, or its function, by pharmacological or genetic means rescues PTP1B activity in insulin-treated cells. These observations uncover novel mechanisms that explain how insulin amplifies the motogenic capacity of the pivotal growth factor PDGF.
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PMID:Chronic insulin treatment amplifies PDGF-induced motility in differentiated aortic smooth muscle cells by suppressing the expression and function of PTP1B. 1845 32


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