BACKGROUND: Effects of angiotensin II type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus ...

Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, lead to increased polyol pathway flux, activation of protein kinase C and accelerated non-enzymatic formation of advanced glycation end products. Many of these pathways become activated in response to the production of superoxide anion. Superoxide can interact with nitric oxide, forming ...

A number of population studies have suggested that hyperinsulinaemia is an independent risk factor for the development of cardiovascular atherosclerosis. Furthermore, there is an emerging body of evidence supporting a role for insulin as both a vasoregulatory and glucoregulatory peptide. Principal amongst insulin's putative vascular effects is to stimulate release ...

Hyperglycemia is a causal factor in the development of the vascular complications of diabetes. One of the biochemical mechanisms activated by excess glucose is the polyol pathway, the key enzyme of which, aldose reductase, transforms d-glucose into d-sorbitol, leading to imbalances of intracellular homeostasis. We aimed at verifying the effects ...

C-reactive protein (CRP) is a non-specific biomarker of inflammation. Recent research has shown that inflammation is an important step in the genesis of atherosclerosis, and is involved in the development of unstable plaques. Measurement of serum levels of CRP using a high sensitivity assay (hsCRP) can demonstrate subclinical inflammatory states, ...

The study has been designed to investigate the effect of Bis-(maltolato) oxovanadium (BMOV), an inhibitor of protein tyrosin phosphatase (PTPase), in diabetes mellitus and hyperhomocysteinemia induced vascular endothelial dysfunction. Streptozotocin (55 mg kg(-1), i.v.) and methionine (1.7% w/w, p.o., 4 weeks) were administered to rats to produce diabetes mellitus (serum ...

Obesity and type 2 diabetes have reached epidemic proportions worldwide. It is known that diabetics have a significantly increased risk for developing cardiovascular disease, especially coronary artery disease. The coronary circulation is regulated cooperatively by numerous systems including the vasodilator nitric oxide (NO) system and the vasoconstrictor endothelin-1 (ET-1) and ...

Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements ...

The main etiology for mortality and a great percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The pathogenesis of cardiovascular disease (CVD) in diabetes is multifactorial and can be affected by metabolic and other factors. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically ...

The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without ...

OBJECTIVE: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed ...

Diabetes mellitus is associated with disturbed regulation in the microcirculation. A low-grade vascular inflammation has been implicated in the development of diabetes-related vascular complications, but the underlying molecular mechanisms has not yet been fully elucidated. It is known that cyclooxygenase-2 (COX-2) plays a key role in prostaglandin biosynthesis during the ...

Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With the worldwide increase in the ...

Although microvascular complications are frequent in diabetes, the pathogenesis underlying these morbidities remains unclear. Chronic inflammation appears to play a role both in the development of vascular dysfunction and diabetes. Evaluation of microvascular status in the prediabetic stages would provide a better insight into the natural progression of the disease, ...

Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive agents. Phosphatidylinositol 3-kinase (PI3K) is a signalling enzyme that plays key roles in vascular growth, proliferation and cellular apoptosis and is implicated in modulating vascular smooth muscle ...

Vascular complications, including impaired contractility and increased cell proliferation, are the most common complications with diabetes. Chronic hyperglycemia seems to be an important contributing factor in this process. Various signaling pathways are implicated in diabetes/hyperglycemia-induced impaired vascular functions. Nonenzymatic glycation, enhanced production of diacylglycerol, increased activity of membranous protein kinase ...

Diabetes mellitus increases the risk of cerebrovascular disease, the effects of hypercapnia on CBF (cerebral blood flow) and cerebrovascular reactivity during diabetes are still inconsistent. Here, we have established a new microangiographic technique using synchrotron radiation (SPring-8, Japan), which enabled us to visualize rat cerebral vessels with high spatial resolution ...

Diabetes mellitus is a main risk factor for vascular diseases. Vascular injury induced by diabetes mellitus is characterized by endothelial dysfunction attributable to an increased oxidative stress. So far, the molecular mechanisms involved in the vasculotoxic effects of diabetes are only partially known. We examined the effect of diabetes mellitus ...

Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later ...

Cardiovascular complications account for significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy, a prominent cardiovascular complication, has been recognized as a microvascular disease that may lead to heart failure. Pathogenesis of diabetic cardiomyopathy involves vascular endothelial cell dysfunction, as well as myocyte necrosis. Clinical trials have identified hyperglycemia ...

OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function ...

The paper deals with pharmacotherapeutical approaches to decreasing hematocrit in order to improve macro and microcirculation in arteries of lower limbs of type 2 diabetes patients. The study included 37 patients with diabetic angiopathy, all of whom had inoperable changes to arteries. In order to decrease hematocrit and cause haemodilution, ...

We investigated the effect of insulin on basal tone and contractile response in isolated aorta from hypertensive streptozotocin-induced diabetic rats (DR) and the role of endothelium in this response. The effect of insulin was tested in rings of control rats (CR) and DR in different protocols: in basal tone, in ...

Although it is well established that diabetes impairs endothelium-dependent vasodilation, including those pathways involving vascular myocyte large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), little is known about the effects of diabetes on BK(Ca) activation as an intrinsic response to contractile stimulation. We have investigated this mechanism in a model of Type 2 ...

Diabetes mellitus is a major and increasing health problem worldwide. One of the most serious consequences of diabetes is the development of diabetic angiopathy, which includes cardiovascular disease, neuropathy, retinopathy and nephropathy. Diabetic nephropathy alone affects 15-25% of patients with type 1 diabetes and 30-40% of patients with type 2 ...

Endothelial progenitor cells (EPC) have been shown to contribute to neovascularization and vascular maintenance and repair in adults. Recently, the concept has evolved that EPC dysfunction, in patients at risk for cardiovascular disease, may contribute to the development of atherosclerosis and ischemic vascular disease. Particularly, patients with diabetes mellitus are ...

OBJECTIVE: The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels ...

Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-alpha that is highly expressed in skeletal muscle and heart, where it promotes beta-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-alpha regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, ...

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), ...

The middle meningeal vascular network leaves its traces on the endocranial surface because of the tight relationship between neurocranial development and brain growth. Analysing the endocast of fossil specimens, it is therefore possible to describe the morphology of these structures, leading inferences on the cerebral physiology and metabolism in extinct ...

Receptor for advanced glycation end product (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. The ligand-RAGE axis is emerging as a central mechanism linked to vascular injury and atherosclerosis in diabetes and in euglycemia. The repertoire of RAGE ligands, including advanced glycation end products, S100/calgranulins, high-mobility ...

We tested the hypothesis that impaired peripheral circulation in diabetes arises from different aspects of vascular abnormalities even when accompanied by a normal ankle-brachial index (ABI>0.9). One hundred fourteen type 2 diabetic patients with normal ABI and 33 age-matched non-diabetic subjects consecutively admitted to our hospital were enrolled. The Agatston ...

OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic insulin resistance. METHOD AND RESULTS: Twenty obese patients with type 2 diabetes were randomized ...

OBJECTIVES: The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabetic patients with chronic coronary heart disease (CHD). BACKGROUND: Diabetes is characterized by a decreased collateral vessel formation in response to coronary ischemic events, although ...

Alpinia zerumbet (K. Schum), a medicinal plant originated from West Asia, is used in the northeast and southeast of Brazil as infusions or decoctions as a diuretic, antihypertensive, and antiulcerogenic. Experiments were undertaken to determine whether a hydroalcoholic extract obtained from leaves of Alpinia zerumbet (AZE) induces vasodilation in the ...

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor ...

BACKGROUND: The renin-angiotensin system plays an important role in the pathogenesis of diabetes-induced vascular and renal complications. Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase. OBJECTIVE: To compare the effectiveness of vasopeptidase inhibition and ACE inhibition in preventing hypertension, endothelial dysfunction and diabetic nephropathy in spontaneously diabetic Goto-Kakizaki ...

The risk of cerebrovascular disease is four- to sixfold higher in patients with diabetes. Vascular remodeling, characterized by extracellular matrix deposition and an increased media-to-lumen ratio, occurs in diabetes and contributes to the development of complications. However, diabetes-induced changes in the cerebrovascular structure remain unknown. Endothelin-1 (ET-1), a potent vasoconstrictor ...

Thiazolidinediones (TZDs), which are synthetic ligands for peroxisome proliferator activated receptor g (PPARg) activation, have been introduced in clinical medicine to improve insulin resistance and glycemic control in patients with type 2 diabetes. The metabolic effects of TZDs are mediated by receptor-dependent activation of the PPARg-retinoid X receptor (RXR) complex ...

Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals ...

OBJECTIVE: Small vessel disease is more common in Afro-Caribbeans than Caucasians. We investigated underlying differences in metabolic, inflammatory, and vascular responses that may predispose Afro-Caribbeans to small vessel pathology. METHODS AND RESULTS: Seventy-eight Afro-Caribbeans aged 35-75 years, with no vascular disease or medications, were compared with 82 matched Caucasians for ...

The effects of high glucose on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations of isolated rat mesenteric artery and the possible involvement of reactive oxygen species in these responses were investigated. After precontraction with phenylephrine (3 x 10(-8)-10(-7) M), acetylcholine (10(-8)-3 x 10(-6) M) and A 23187 (10(-8)-3 x 10(-6) M), a ...

High glucose-induced apoptosis in vascular endothelial cells may contribute to the acceleration of atherosclerosis associated with diabetes. Here, we show that erythropoietin attenuates high glucose-induced apoptosis in cultured human aortic endothelial cells (HAECs). Exposure of HAECs to high glucose level for 72h significantly increased the number of apoptotic cells compared ...

Elevated plasma glucose, as commonly seen in types I and II diabetes mellitus, is known to result in endothelial dysfunction, a condition characterized by a loss of nitric oxide (NO)-dependent regulation of vascular tone. In the present study, we have utilized a recently developed NO-sensitive fluorescent dye, DAF-FM (4-amino-5-methylamino-2',7'-difluorofluorescein) diacetate ...

CONTEXT: The contribution of insulin resistance per se to the vascular risk conferred by the metabolic syndrome (MetS) is not known; conversely, it is uncertain whether insulin resistance confers vascular risk beyond the entity of the MetS. OBJECTIVE: The objective of this study was to investigate the impact of the ...

Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding ...

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This ...

BACKGROUND AND AIM: In vivo and in vitro experimental findings indicate that the hyperglycemic diabetic milieu can induce altered expression of the matrix metalloproteinase (MMP) genes and contribute to imbalances in vascular matrix homeostasis. We examined the plasma levels of enzymes and inhibitors involved in extracellular matrix turnover. METHODS: We ...

The endothelium is a complex organ with a multitude of properties essential for control of vascular functions. Dysfunction of the vascular endothelium is regarded as an important factor in the pathogenesis of diabetic micro- and macro-angiopathy. Endothelial dysfunction in Type I and II diabetes complicated by micro- or macro-albuminuria is ...

Diabetes is associated with a perturbation of signaling pathways in vascular tissue, which causes vasomotor dysfunction such as hypertension and accelerated atherosclerosis. In the present study, the mechanisms of vasomotor dysfunction, Akt (Thr308 and Ser473) phosphorylation and expression of endothelial NO (nitric oxide) synthase, and inducible NO synthase were investigated ...