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

Robert Furchgott's discovery of the obligatory role that the endothelium plays in the regulation of vascular tone has proved to be a major advance in terms of our understanding of the cellular basis of diabetic vascular disease. Endothelial dysfunction, as defined by a reduction in the vasodilatation response to an endothelium-dependent vasodilator (such as acetylcholine) or to flow-mediated vasodilatation, is an early indicator for the development of the micro- and macroangipathy that is associated with diabetes. In diabetes, hyperglycaemia plays a key role in the initiation and development of endothelial dysfunction; however, the cellular mechanisms involved as well as the importance of dyslipidaemia and co-morbidities such as hypertension and obesity remain incompletely understood. In this review, we discuss the mechanisms whereby hyperglycaemia, oxidative stress and dyslipidaemia can alter endothelial function and highlight their effects on endothelial nitric oxide synthase (eNOS), the endothelium-dependent hyperpolarising factor (EDHF) pathway(s), as well as on the role of endothelium-derived contracting factors (EDCFs) and adipocyte-derived vasoactive factors such as adipose-derived relaxing factor (ADRF).
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PMID:Endothelial dysfunction in diabetes: multiple targets for treatment. 2023 24

Prehypertension is a highly frequent condition associated with an increased cardiovascular risk. Endothelial dysfunction is thought to promote the development of hypertension and vascular disease; however, underlying mechanisms remain to be further determined. The present study characterizes for the first time the in vivo endothelial repair capacity of early endothelial progenitor cells (EPCs) in patients with prehypertension/hypertension and examines its relation with endothelial function. Early EPCs were isolated from healthy subjects and newly diagnosed prehypertensive and hypertensive patients (n=52). In vivo endothelial repair capacity of EPCs was examined by transplantation into a nude mouse carotid injury model. EPC senescence was determined (RT-PCR of telomere length). NO and superoxide production of EPCs were measured using electron spin resonance spectroscopy analysis. CD34(+)/KDR(+) mononuclear cells and circulating endothelial microparticles were examined by fluorescence-activated cell sorter analysis. Endothelium-dependent and -independent vasodilations were determined by high-resolution ultrasound. In vivo endothelial repair capacity of EPCs was substantially impaired in prehypertensive/hypertensive patients as compared with healthy subjects (re-endothelialized area: 15+/-3%/13+/-2% versus 28+/-3%; P<0.05 versus healthy subjects). Senescence of EPCs in prehypertension/hypertension was substantially increased, and NO production was markedly reduced. Moreover, reduced endothelial repair capacity of early EPCs was significantly related to an accelerated senescence of early EPCs and impaired endothelial function. The present study demonstrates for the first time that in vivo endothelial repair capacity of early EPCs is reduced in patients with prehypertension and hypertension, is related to EPC senescence and impaired endothelial function, and likely represents an early event in the development of hypertension.
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PMID:Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. 2045 6

Thromboangiitis obliterans (also known as Buerger's disease) is an inflammatory vascular disorder that affects small and medium-sized arteries and veins in the extremities. There is no specific treatment and the only effective intervention is absolute cessation of tobacco use. Endothelial dysfunction appears to be of relevance to this condition and a report has even found that high serum levels of endothelin correlate with the presence of necrosis. We report two cases of digital necrosis showing a very satisfactory response to treatment with bosentan, a dual endothelin receptor antagonist.
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PMID:Efficacy of bosentan in digital ischemic ulcers. 2057 85

Endothelial dysfunction is regarded as an important factor in the pathogenesis of vascular disease in obesity-related type 2 diabetes. The imbalance in repair and injury (hyperglycemia, hypertension, dyslipidemia) results in microvascular changes, including apoptosis of microvascular cells, ultimately leading to diabetes related complications. This review summarizes the mechanisms by which the interplay between endothelial dysfunction, inflammation, and apoptosis may cause (micro)vascular damage in patients with diabetes mellitus.
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PMID:Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. 2063 40

Cardiovascular disease is a very early phenomenon in the course of chronic renal failure, and increases continuously with decrease of renal function. Endothelial dysfunction seems to be a starting point in vascular changes leading to atherosclerosis and artery calcification. Endothelium, considered the largest organ in the body, has many functions. It senses mechanical and hormonal stimuli and in response the endothelial cells secrete a range of compounds which modulate vascular tone, coagulation, cell proliferation, and inflammation. The central role of endothelium in the development of vascular disease has led to identification of new relevant biomarkers and methods to estimate endothelial function and injury. Arterial stiffness, which is not an early phenomenon in endothelial dysfunction but a common complication of chronic renal failure may be evaluated through Pulse Wave Velocity and Augmentation Index obtained by pulse-wave analysis. Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality in patients with hypertension. A new fascinating aspect of research in endothelial function is rising through the studies on endothelial progenitor cells. These are primitive bone marrow cells that have the ability to mature into endothelial cells and have a physiologic role in the repair of endothelial lesions.
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PMID:Endothelial dysfunction in chronic renal failure. 2079 56

Current theories state that Alzheimer's disease (AD) is a vascular disorder that initiates its pathology through cerebral microvascular abnormalities. Endothelial dysfunction caused by the injury or death of endothelial cells contributes to progression of AD. Also, functional relationships between neurons, glial cells, and vascular cells within so-called neurovascular unit are dramatically compromised in AD. Several recent studies have highlighted that endothelial cells might be the target for the toxic action of heavily aggregated proteins, glia-derived cytokines, and stimuli inducing oxidative and metabolic stress in AD brains. Here, we describe the properties of the brain endothelium that contribute to its specific functions in the central nervous system, and how endothelial-neuronal-glial cell interactions are compromised in the pathogenesis of AD. We also discuss the ways in which functioning of endothelial cells can be modulated in cerebral microvessels. Understanding of molecular mechanisms of endothelial injury and repair in AD would give us novel diagnostic biomarkers and pharmacological targets.
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PMID:Endothelial dysfunction and repair in Alzheimer-type neurodegeneration: neuronal and glial control. 2084 14

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. This condition increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease fourfold. Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus patients and has recently received increased attention. In this review article, some recent developments that could improve the knowledge of diabetes-induced endothelial dysfunction are discussed.
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PMID:Novel mechanisms of endothelial dysfunction in diabetes. 2087 87

Endothelial dysfunction leads to lethal vascular complications in diabetes and related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane. In mice with endothelial inactivation of FAS (FASTie mice), eNOS membrane content and activity were decreased. eNOS and FAS were physically associated; eNOS palmitoylation was decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS-associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory state reflected as increases in vascular permeability, endothelial inflammatory markers, leukocyte migration, and susceptibility to LPS-induced death that was reversed with an NO donor. FAS-deficient endothelial cells showed deficient migratory capacity, and angiogenesis was decreased in FASTie mice subjected to hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through impaired lipogenesis identifies a novel mechanism coordinating nutritional status and tissue repair that may contribute to diabetic vascular disease.
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PMID:De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase (eNOS) palmitoylation. 2109 89

The endothelium is a single layer of cells lining all blood vessels. Although the endothelium is not an organ it does, nonetheless have autocrine, paracrine and endocrine-like functions that affect the cardiovascular system. Until the description in 1980 by Nobel Laureate Robert Furchgott of endothelium-derived relaxing factor (EDRF), later identified as nitric oxide (NO), the endothelium was considered to be a semi-permeable barrier between the blood and the smooth muscle cell layers of the blood vessel. Heterogeneity exists in the functions of the endothelium with differences evident between species and between the large conduit compliance vessels and the resistance vessels of the microcirculation. Endothelial dysfunction, defined as a reduction in the ability of the endothelium to transmit a vasodilatation influence on blood flow, has prognostic significance and serves as an early indicator of the development of vascular disease as well as a therapeutic target. This review compares the role of the endothelium in the regulation of vascular tone in conduit versus resistance vessels and how alterations in endothelial function may lead to vascular disease.
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PMID:The endothelium in compliance and resistance vessels. 2119 8

Endothelial dysfunction is a key event in the development of vascular disease, and it precedes clinically obvious vascular pathology. Abnormal activation of the RhoA/Rho kinase (ROCK) pathway has been found to elevate vascular tone through unbalancing the production of vasodilating and vasoconstricting substances. Inhibition of the RhoA/ROCK pathway can prevent endothelial dysfunction in a variety of pathological conditions. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of the ROCK pathway and its roles in endothelial dysfunction.
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PMID:The role of RhoA/Rho kinase pathway in endothelial dysfunction. 2126 79


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