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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic physiological functions of the endothelium are functions of a semipermeable membrane, control of optimal vascular patency and safeguarding of the vascular integrity. Endothelial dysfunction may be considered the first functionally important stage of atherosclerosis. The most frequent evoking factors include hyperlipoproteinaemia, arterial hypertension, smoking and diabetes mellitus. The clinically most important manifestations of impaired endothelial function are disorders in the coronary circulation and transient cerebral ischaemias. Ways of detection of endothelial dysfunctions include invasive methods and at present non-invasive ultrasonic methods. Treatment of endothelial dysfunction is based on elimination of the basic risk factors of atherosclerosis, i.e. elimination of active and passive smoking, in indicated cases strict dietetetic and pharmacological hypolipidaemic treatment, effective antihypertensive treatment and compensation of DM.
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PMID:[Vascular endothelial dysfunctions, possible detection and treatment]. 1563 2

Erectile dysfunction (ED) is more commonly seen in men with various components of the metabolic syndrome (a constellation of various cardiovascular and diabetes risk factors). ED can be considered as a risk marker of the metabolic syndrome and its associated conditions. The patient with ED should be thoroughly evaluated for coexisting vascular disease. Any cardiovascular risk factors should be modified or treated (ie, smoking, diabetes, hypertension, and hyperlipidemia). Endothelial dysfunction is a major unifying etiology for many of the aspects of the metabolic syndrome, especially diabetes and cardiovascular disease. It also plays a major role in ED. The multifactorial etiology of ED, especially in patients with the metabolic syndrome, increases the complexity of managing this problem so clinicians need to be aware of the underlying pathophysiology to ensure the best possible outcomes in management.
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PMID:Erectile dysfunction: interrelationship with the metabolic syndrome. 1566 20

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.
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PMID:Clinical aspects of reactive oxygen and nitrogen species. 1577 17

Cardiovascular complications are the leading cause of morbidity and mortality in diabetic patients. Endothelial dysfunction with impaired endothelial nitric oxide (NO) synthase (eNOS) activity is a widely accepted cause of diabetic vasculopathy. The mechanisms of endothelial dysfunction in diabetes remain elusive, thus limiting effective therapeutic interventions. We report novel evidence demonstrating that the calcium-dependent protease calpain causes endothelial dysfunction and vascular inflammation in the microcirculation of the ZDF (Zucker diabetic fatty) rat, a genetic rat model of type 2 diabetes. We found evidence of increased calpain activity and leukocyte trafficking in the microcirculation of ZDF rats. Inhibition of calpain activity significantly attenuated leukocyte-endothelium interactions in the vasculature of ZDF rats. Expression of cell adhesion molecules in the vascular endothelium of ZDF rats was consistently increased, and it was suppressed by calpain inhibition. In vivo measurement of endothelial NO availability demonstrated a 60% decrease in NO levels in the microcirculation of diabetic rats, which was also prevented by calpain inhibition. Immunoprecipitation studies revealed calpain-dependent loss of association between eNOS and the regulatory protein heat shock protein 90. Collectively, these data provide evidence for a novel mechanism of endothelial dysfunction and vascular inflammation in diabetes. Calpains may represent a new molecular target for the prevention and treatment of diabetic vascular complications.
Diabetes 2005 Apr
PMID:The calcium-dependent protease calpain causes endothelial dysfunction in type 2 diabetes. 1579 53

Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E-selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E-selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin A(1c)) in 719 nondiabetic participants of the Nurses' Health Study or with risk of diabetes in 602 incident (over 10 years of follow-up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E-selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E-selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C-reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor-adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E-selectin variants we examined are not important genetic risk factors for type 2 diabetes in women.
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PMID:E-selectin genotypes and risk of type 2 diabetes in women. 1628 35

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

Recent large clinical trials have shown that angiotensin II type I receptor blockers (ARBs) reduce cardiovascular morbidity and mortality in patients with heart failure, acute myocardial infarction, and hypertension. However, the mechanism underlying antiatherogenic effects of ARBs remains unclear. The vascular endothelium is involved in the release of various vasodilators, including nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in the regulation of vascular tone, the inhibition of platelet aggregation, and the suppression of smooth muscle cell proliferation. Several investigators have reported impairment in endothelium-dependent vasodilation in the forearm, coronary, and renal vasculature in cardiovascular diseases, including hypertensive patients. Cardiovascular diseases are associated with alteration in endothelial function. Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis. Anti-renin-angiotensin system agents, angiotensin-converting enzyme (ACE) inhibitors improve endothelial function in patients with hypertension, diabetes mellitus, and coronary artery disease. It is well known that ACE inhibitors augment endothelium-dependent vasodilation through an increase in NO bioavailability, by an increase in NO production and a decrease in NO inactivation. ARBs are also thought to prevent cardiovascular complications through an augmentation of endothelial function. In this review, we focus on recent findings and putative mechanisms of the beneficial effects of ARBs on endothelial function.
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PMID:Angiotensin II type I receptor blocker and endothelial function in humans: role of nitric oxide and oxidative stress. 1585

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species (ROS), such as the superoxide radical, and the subsequent decrease in vascular bioavailability of nitric oxide (NO). Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include the NAD(P)H oxidase, the xanthine oxidase, and mitochondrial superoxide-producing enzymes. Superoxide produced by the NADPH oxidase may react with NO released by endothelial nitric oxide synthase (eNOS), thereby generating peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, thereby switching an antiatherosclerotic NO-producing enzyme to an enzyme that may initiate or even accelerate the atherosclerotic process by producing superoxide. Increased oxidative stress in the vasculature, however, is not restricted to the endothelium and has also been demonstrated to occur within the smooth muscle cell layer in the setting of hypercholesterolemia, diabetes mellitus, hypertension, congestive heart failure, and nitrate tolerance. Increased superoxide production by the endothelial and/or smooth muscle cells has important consequences with respect to signaling by the soluble guanylyl cyclase (sGC) and the cGMP-dependent protein kinase I (cGK-I), the activity and expression of which has been shown to be regulated in a redox-sensitive fashion. The present review summarizes current concepts concerning eNOS uncoupling and also focuses on the consequences for downstream signaling with respect to activity and expression of the sGC and cGK-I in various diseases.
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PMID:Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. 1587 5

Over the last two decades, it has become evident that the endothelium is more than an inert, single-cell lining covering the internal surface of blood vessels. Normally, the endothelium actively decreases vascular tone, maintains vascular permeability within narrow bounds, inhibits platelet adhesion and aggregation, limits activation of the coagulation system, and stimulates fibrinolysis. Endothelium dysfunction can be considered present when its functions, either in the basal state or after stimulation, are altered in a way that is inappropriate to the preservation of organ function. Endothelial dysfunction has been associated to many cardiovascular risk factors including diabetes, hypertension and hypercholesterolemia. In addition, endothelial dysfunction may play a crucial role in the development and progression of atherosclerosis. This review will give a brief overview of the different methods to assess endothelial function, and then will focus on the current knowledge on soluble cellular adhesion molecules in relation to the metabolic syndrome and type 2 diabetes.
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PMID:Endothelial dysfunction, cellular adhesion molecules and the metabolic syndrome. 1591 11

Endothelial dysfunction and reduced BRS (baroreflex sensitivity) may be present in patients with CAD (coronary artery disease). The normal fasting glucose level does not exclude abnormal glucose metabolism in patients with CAD. The aim of present study was to evaluate endothelial function and BRS according to glucose metabolism in patients with normal fasting plasma glucose and stable CAD subjected to PTCA (percutaneous transluminal coronary angioplasty). Forty-six consecutive patients who underwent elective PTCA were studied (37 men; mean age 56 years). Endothelial function was assessed non-invasively using the arterial vasodilator response to salbutamol (albuterol). BRS was measured using a cross-correlation method. The extent of coronary narrowing was estimated by calculation of the Gensini score. All patients underwent a 75 g OGTT (oral glucose tolerance test). IGT (impaired glucose tolerance) or diabetes was present in approx. 60% of patients. The vasodilator response to salbutamol, as a measure of endothelial dysfunction, was significantly impaired in patients with IGT or diabetes compared with those with normal glucose tolerance (-0.5+/-1.6% compared with -7.9+/-2.2; P=0.01). Glucose metabolism and age were significant predictors of endothelial dysfunction (R(2)=35.2%, P=0.02). BRS did not differ significantly between patients with normal glucose tolerance and those with IGT or diabetes (6.9+/-1.2 compared with 6.1+/-0.6 ms/mmHg respectively; P=0.669). BRS was negatively correlated with age (r=-0.34, P=0.021) and the Gensini score (r=-0.34, P=0.022). The significant predictors of BRS were Gensini score, age and past myocardial infarction (R(2)=37.02%, P=0.002). Patients with established CAD, normal fasting glucose and IGT or diabetes demonstrated impaired endothelial function which did not correlate with the extent of coronary artery involvement. Conversely, BRS in the study population was not affected by glucose metabolism, but showed an interaction with the extent of coronary narrowing.
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PMID:Endothelial function and baroreflex sensitivity according to the oral glucose tolerance test in patients with coronary artery disease and normal fasting glucose levels. 1594 15


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