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

Polycystic ovary syndrome (PCOS), a syndrome of hyperandrogenism and anovulation with numerous associated derangements, is typified by a substantially increased incidence of type 2 diabetes mellitus and coronary disease in mid-adult life. A marker of the disorder, and a potential determinant of the macroangiopathy, is insulin resistance. Thus, in addition to altered lipid metabolism, hypertension, hormonal derangements, obesity, and altered coagulation--all of which may contribute to the development of vascular disease--the insulin resistance and dysinsulinemia may underlie impaired fibrinolysis and related derangements within the vessel walls that may be modifiable by attenuation of insulin resistance and amelioration of hyperinsulinemia.
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PMID:Cardiovascular consequences of polycystic ovary syndrome. 1035 28

Human obesity is associated with insulin resistance, hyperinsulinemia, and a predisposition to hypertension and vascular disease, the origin of which may lie in impairment of endothelial function. We tested the effects of the thiazolidinedione rosiglitazone on blood pressure and endothelial function in insulin-resistant fatty Zucker rats, which display hypertension and abnormal endothelial cell function. We studied fatty Zucker rats given rosiglitazone maleate (50 micromol/kg diet; n = 8) for 9-12 weeks (treated fatty), untreated fatty rats (n = 8), and lean rats (n = 8) given diet alone. At the end of the study, systolic blood pressure was significantly higher in untreated fatty (147 +/- 5 mmHg) than in lean rats (125 +/- 2 mmHg; P < 0.05), but rosiglitazone treatment prevented the development of hypertension in fatty rats (123 +/- 1 mmHg). Fasting hyperinsulinemia in untreated fatty rats (28.7 +/- 6.0 ng/ml) was significantly lowered by rosiglitazone (7.0 +/- 1.4 ng/ml; P < 0.05 vs. untreated fatty), but remained significantly higher than the levels seen in lean rats (1.5 +/- 0.4 ng/ml; P < 0.01). Mesenteric arteries were studied in a myograph. Maximal acetylcholine chloride (1.1 micromol/l)-induced relaxation of norepinephrine hydrochloride (NE)-induced constriction was impaired in untreated fatty (62.4 +/- 3.4%) vs. lean (74.3 +/- 3.5%; P = 0.01) rats; this defect was partially prevented by rosiglitazone (66.5 +/- 3.0%; P = 0.01 vs. untreated fatty). Insulin (50 mU/l) significantly attenuated the contractile response to NE in lean rats (14.7 +/- 3.3%; P = 0.02); this vasodilator effect of insulin was absent in untreated fatty rats at concentrations of 50-5,000 mU/l, but was partially restored by rosiglitazone (9.7 +/- 2.5% attenuation; P = 0.02 vs. no insulin). Thus, rosiglitazone prevents the development of hypertension and partially protects against impaired endothelial function associated with insulin resistance. These latter effects may contribute to the drug's antihypertensive properties.
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PMID:The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. 1038 52

Insulin resistance emerges as a central component of the risk factor cluster and is a likely contributor to vascular disease independently of traditional risk factors such as hypertension and diabetes mellitus. However, the intermediary mechanisms by which atherosclerosis is accelerated among patients with the insulin resistance syndrome remain inadequately defined. Most of the attention has centered on hyperinsulinemia and defects of insulin-mediated glucose disposal. However, we observed that obese hypertensive patients have elevated plasma concentrations of non-esterified fatty acids (NEFAs), including oleic acid, which are highly resistant to suppression by insulin. Resistance to insulin's fatty acid lowering action correlate with blood pressure in obese subjects independently of defects in glucose disposal. This observation raises the possibility that NEFAs have biologically significant effects on the cardiovascular system. In fact, oleic acid impairs nitric oxide synthase activity and endothelium-dependent vasorelaxation in vitro. Moreover, raising NEFAs in normal human volunteers to levels observed in obese hypertensive patients impairs lower extremity endothelium-dependent vasodilation and augments local and systemic vascular alpha1-adrenoceptor reactivity in normal volunteers. Thus, raising NEFAs replicates in healthy subjects important functional vascular changes implicated in the hypertension and atherosclerosis observed in patients with the risk factor cluster. At a molecular level, experiments in cultured vascular smooth muscle cells demonstrate that oleic acid activates a mitogenic signaling cascade which includes protein kinase C, reactive oxygen species and extracellular signal-regulated kinases. Each of these signaling events has been implicated in the structural and functional vascular changes which accompany the risk factor cluster. Collectively, these observations raise the possibility that fatty acids contribute to functional and structural vascular changes among insulin-resistant individuals. A better understanding of the signaling mechanisms by which NEFAs exert their vascular effects may facilitate novel and more effective therapeutic approaches to managing the cardiovascular risk factor cluster.
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PMID:Vascular effects of non-esterified fatty acids: implications for the cardiovascular risk factor cluster. 1047 Nov 31

Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease.
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PMID:Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia. 1059 80

The hypothesis that vascular factors may contribute to the development of Alzheimer's disease (AD) is supported by epidemiologic and pathologic observations. Arterial hypertension and diabetes have been found to be associated not only with vascular dementia, but also with AD; in addition, the treatment of hypertension with calcium antagonists seems to prevent degenerative dementias. Hypertension and hyperinsulinemia favor the deposition of amyloid substance in the brain. The histopathology of AD is marked not only by neurofibrillary tangles and senile plaques, but also by macro and micro congophilic angiopathy and ischemic white matter rarefaction. The specific AD pathological lesions, if isolated, are not able to lead to an evident clinical picture of dementia, which, on the contrary, becomes evident when vascular, mainly subcortical, lesions are associated. These and other observations suggest that vascular factors may have a role in the development of AD. An aggressive approach to these factors could be of value in the prevention of AD.
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PMID:Are vascular factors involved in Alzheimer's disease? Facts and theories. 1073 48

The fatty liver dystrophy (fld) mutant mouse is characterized by neonatal fatty liver and hypertriglyceridemia that resolve at weaning, and neuropathy affecting peripheral nerve in adulthood. We now report additional significant manifestations of this single gene mutation, which include adipose tissue deficiency, glucose intolerance, and increased susceptibility to atherosclerosis. In adult fld/fld mice, both white and brown fat pads exhibit an 80% reduction in mass compared with wild-type controls, and consist of immature adipocytes as assessed by morphological and molecular criteria. The lack of lipid accumulation in fld/fld adipose tissue could be attributed, in part, to a failure to induce expression of lipoprotein lipase and enzymes involved in fatty acid synthesis, such as fatty acid synthase and acetyl-CoA carboxylase. Related to the deficiency of adipose tissue, fld/fld mice were also found to exhibit profound glucose intolerance, modest hyperinsulinemia, and reduced tissue response to insulin. As insulin resistance is a important risk factor in vascular disease, we examined susceptibility of fld/fld mice to diet-induced atherosclerosis. Mutant mice fed an atherogenic diet developed 2-fold greater aortic lesions than their wild-type counterparts, despite having a less atherogenic lipoprotein cholesterol profile. The fld adipose-deficient phenotype has both similarities to and distinctions from the group of rare human diseases known as lipodystrophies.
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PMID:Adipose tissue deficiency, glucose intolerance, and increased atherosclerosis result from mutation in the mouse fatty liver dystrophy (fld) gene. 1088 87

The western way of life favours the development of a state of insulin resistance, in genetically predisposed subjects. In this state, greater levels of insulin are necessary so that an answer can be obtained and, consequently, hyperinsulinism occurs. Insulin has several target tissues, thus insulin resistance is associated with the dysfunction of a multiplicity of tissues, organs and systems in the body (Syndrome X). All of those dysfunctions together with hyperinsulinism can greatly enhance the risk of atherosclerotic vascular disease. In this article we review the dysfunction at several levels, including blood pressure, endothelium, lipid metabolism and fibrinolytic system and the way they can, together with hyperinsulinism, induce atherogenesis. We review some of the therapeutic options that can reduce this state of insulin resistance as well as the morbidity and mortality associated with atherosclerosis.
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PMID:[Insulin resistance and atherosclerosis]. 1115 88

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS. Further properly planned randomised controlled trials are required.
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PMID:Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group. 1145 23

Insulin resistance is associated with an increased risk of atherothrombotic vascular disease, but the mechanisms are poorly understood. We determined how insulin in vivo regulates platelet activation in nonobese and obese subjects by using methods mimicking thrombus formation. Twelve nonobese (aged 42+/-2 years, body mass index 24.0+/-0.4 kg/m(2)) and 14 obese (aged 43+/-1 years, body mass index 37.2+/-1.5 kg/m(2)) subjects were studied under euglycemic hyperinsulinemic (3-hour insulin infusion of 1 mU. kg(-1). min(-1)) conditions. Before and at the end of hyperinsulinemia, the following were determined: (1) platelet-related early hemostasis (shear rate of approximately 4000 s(-1)) by platelet function analysis; (2) platelet deposition to collagen during whole-blood perfusion (shear rate of 1600 s(-1)); (3) aggregation responses to collagen, thrombin receptor-activating peptide, ADP, and epinephrine; and (4) platelet cGMP concentrations. Insulin action on glucose metabolism was 69% lower in the obese subjects (1.6+/-0.2 mg. kg(-1). min(-1)) than in the nonobese subjects (5.4+/-0.4 mg. kg(-1). min(-1), P<0.0001). The in vivo insulin infusion inhibited platelet deposition to collagen from 4.3+/-0.6x10(6) to 3.5+/-0.4x10(6) per square centimeter in the nonobese subjects (P<0.05) but failed to do so in the obese subjects (5.2+/-0.8x10(6) versus 5.5+/-0.7x10(6) per square centimeter, P=NS; P<0.01 versus nonobese subjects). Epinephrine- and ADP-primed closure times by platelet function analysis were prolonged by insulin in the nonobese but not the obese subjects (P<0.05 for between-group difference). In the nonobese subjects, insulin decreased aggregation to all agonists and significantly increased platelet cGMP concentrations (2.5+/-0.3 versus 3.2+/-0.5 pmol/10(9) for before versus after insulin, respectively; P<0.01). In the obese subjects, insulin did not alter collagen-induced aggregation or cGMP concentrations (1.9+/-0.2 versus 1.8+/-0.1 pmol/10(9) for before versus the end of in vivo hyperinsulinemia, respectively; P=NS). These data demonstrate that normal in vivo insulin action inhibits platelet interaction with collagen under conditions mimicking thrombus formation and reduces aggregation to several agonists. These platelet-inhibitory actions of insulin are blunted or absent in obese subjects and could provide 1 mechanism linking insulin resistance to atherothrombotic disease.
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PMID:Inhibition of platelet-collagen interaction: an in vivo action of insulin abolished by insulin resistance in obesity. 1178 78

Although diabetes mellitus is predominantly a metabolic disorder, recent data suggest that it is as much a vascular disorder. Cardiovascular complications are the leading cause of death and disability in patients with diabetes mellitus. A number of recent reports have emphasized that many patients already have atherosclerosis in progression by the time they are diagnosed with clinical evidence of diabetes mellitus. The increased risk of atherosclerosis and cardiovascular complications in diabetic patients is related to the frequently associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and endothelial dysfunction. The evolving knowledge regarding the variety of metabolic, hormonal, and hemodynamic abnormalities in patients with diabetes mellitus has led to efforts designed for early identification of individuals at risk of subsequent disease. It has been suggested that insulin resistance, the key abnormality in type II diabetes, often precedes clinical features of diabetes by 5-6 years. Careful attention to the criteria described for the cardiovascular dysmetabolic syndrome should help identify those at risk at an early stage. The application of nonpharmacologic as well as newer emerging pharmacologic therapies can have beneficial effects in individuals with cardiovascular dysmetabolic syndrome and/or diabetes mellitus by improving insulin sensitivity and related abnormalities. Early identification and implementation of appropriate therapeutic strategies would be necessary to contain the emerging new epidemic of cardiovascular disease related to diabetes.
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PMID:Clinical significance of cardiovascular dysmetabolic syndrome. 1198 76


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