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

Women have been shown to have a lower incidence of vascular disease when compared to men. However, the incidence of vascular disease increases as women progress through menopause and reaches an incidence similar to that of men later in life. Women with peripheral vascular disease often have a delay in diagnosis, a higher incidence of asymptomatic disease, and poorer outcome after interventions. The differences in outcome have been attributed to a number of factors such as anatomic and hormonal differences. It is thought that estrogen deficiency is at least partially responsible for the increased risk of developing vascular disease after menopause, and thus hormone replacement therapy has been considered as a method to prevent progression of vascular disease. Conclusions drawn from a number of recent studies have resulted in a divergent view of hormone replacement therapy (HRT). This article explores the risk of peripheral vascular disease in women and the current state of research on hormone replacement therapy. The aims of this review are to present current perspectives on gender differences in the pathogenesis and outcomes of peripheral arterial disease (PAD). The effect of estrogen on atherogenesis, the role it plays in modulating the vascular endothelium, and the current evidence of the effects of HRT on vascular pathology is discussed. The most recent HRT clinical trials and present evidence for the benefits and risks of postmenopausal hormone replacement therapy are summarized. The effect of these issues on treatment practices is explained and suggestions are made for future directions of HRT and PAD research.
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PMID:Hormone replacement therapy and peripheral vascular disease in women. 1559 36

Changes in plasma protein composition normally associated with malnutrition, specifically hypoalbuminemia and reduced levels of tranferrin and prealbumin, usually only occur in the presence of preterminal starvation in the absence of inflammation. Thus, reduced levels of any of these proteins suggest that the inflammatory response has been activated. Inflammation also alters lipoprotein structure and function, and oxidation of low-density lipoprotein (LDL). This decreases high-density lipoprotein (HDL) levels and reduces its capacity to function as an antioxidant, and increases the levels of proteins, such as fibrinogen, associated with vascular disease. Cytokines and acute phase proteins, such as C-reactive protein (CRP), also up-regulate expression of adhesion molecules on the vascular endothelium, making them more effective targets for macrophage adhesion. Leukocyte-derived myeloperoxidase functions as an "NO oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromises vascular reactivity. The link between inflammation and apparent malnutrition explains the relationship between low levels of albumin, prealbumin, and transferrin with subsequent cardiovascular risk.
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PMID:Effects of inflammation on plasma composition and endothelial structure and function. 1564 15

Hypoalbuminemia is the result of the combined effects of inflammation and inadequate protein and caloric intake in patients with chronic disease such as chronic renal failure. Inflammation and malnutrition both reduce albumin concentration by decreasing its rate of synthesis, while inflammation alone is associated with a greater fractional catabolic rate (FCR) and, when extreme, increased transfer of albumin out of the vascular compartment. A vicious cascade of events ensues in which inflammation induces anorexia and reduces the effective use of dietary protein and energy intake and augments catabolism of the key somatic protein, albumin. Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure, and the major cause of death in this population is due to cardiovascular events. Inflammation is associated with vascular disease and likely causes injury to the vascular endothelium, and hypoalbuminemia as two separate expressions of the inflammatory process. Albumin has a myriad of important physiologic effects that are essential for normal health. However, simply administering albumin to critically ill patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity. Thus the inference from these clinical studies suggests that the cause of hypoalbuminemia, rather than low albumin levels specifically, is responsible for morbidity and mortality.
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PMID:Serum albumin: relationship to inflammation and nutrition. 1566 May 73

An intact vascular endothelium is critical to the maintenance of normal arterial tone and coagulation status. Endothelial injury leading to dysfunction is thought to be a precursor to most if not all vascular disease, and has been implicated as a critical event in atherosclerosis. At present there are several methods available for detection of in vivo endothelial function, and the aim of this study was to critically review these methods. Five distinct methods were identified and studied in detail. These methods are diverse and each assesses a different vascular bed. Importantly there is no uniformity among investigators over choice of method and protocol, making it difficult to compare in vivo enothelial dysfunction between groups. These issues need to be addressed in large scale comparative analyses so that investigators can agree a common approach to endothelial function assessment.
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PMID:A review of methods currently used for assessment of in vivo endothelial function. 1569

In pulmonary vascular disease, changes in the pulmonary vascular bed will lead to altered pulmonary haemodynamics. This review describes the application of several physiological principles to measure these changes noninvasively by means of novel techniques. Flow characteristics of blood through the pulmonary vascular bed alter in pulmonary vascular disease. Recent developments in magnetic resonance imaging and computed tomography make it possible to visualise and quantify these abnormal flow patterns. Information regarding pulmonary perfusion can also be obtained by measuring the electrical impedance changes in the lung by electrical impedance tomography. A more indirect approach to measure the pulmonary blood flow is the measurement of the absorption of acetylene, a perfusion limited gas. Information on the pulmonary vascular bed can also be obtained by the measurement of exhaled products of the pulmonary vascular endothelium, such as nitric oxide. Although all the techniques described offer new ways to diagnose or monitor pulmonary vascular disease, clinical data on these techniques are limited. Further improvement and evaluation of the clinical value of these techniques are therefore obligatory before they can be used in clinical practice.
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PMID:Noninvasive assessment and monitoring of the pulmonary circulation. 1580 53

Selectins (E- and P-selectin) and other endothelial expressed leukocyte adhesion molecules (ELAMs) are potential targets for site-specific delivery of therapeutics to the vascular endothelium due to their specific and highly regulated expression in vascular disease. It was recently shown that degradable microspheres coated with antibodies against E-selectin or other ELAMs can target inflammation in vivo. However, targeting ELAMs alone cannot differentiate between normal and diseased state, as a basal level of these LAMs are expressed on endothelium in healthy tissues. Furthermore, leukocytes usually employ two separate adhesion molecules in parallel to home to diseased tissues, and we recently quantified the advantages of a two-receptor display for the targeting of leukocyte mimetics (Eniola AO, Willcox PJ, Hammer DA. Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor-ligand pairs. Biophys J 2003;85:2720-31). Here, we describe a leukocyte mimetic for targeting therapeutics to the vasculature in inflammatory diseases via two receptors, selectin and intercellular cell adhesion molecule-1 (ICAM-1), where biodegradable, polymer microspheres were co-functionalized with the selectin ligand, sialyl Lewis(X) (sLe(X)), and an antibody against ICAM-1, anti-ICAM-1 (aICAM-1). These two-receptor targeted particles, at given ratios of sLe(X)/aICAM-1, firmly adhere to substrate surface in flow only when both targeting ligands can interact with their respective receptors, mimicking the multi-step in vivo leukocyte adhesion in inflammation. Thus, we have faithfully recreated the specificity and extent of leukocyte adhesion in a platform that can allow for local delivery of therapeutics.
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PMID:In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors. 1595 32

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 generalized in that it affects many aspects of endothelial function and occurs not only in the kidney. The close linkage between microalbuminuria and endothelial dysfunction in diabetes is an attractive explanation for the fact that microalbuminuria is a risk marker for atherothrombosis. In Type I diabetes, endothelial dysfunction precedes and may cause diabetic microangiopathy, but it is not clear whether endothelial dysfunction is a feature of the diabetic state itself. In Type II diabetes, endothelial function is impaired from the onset of the disease and is strongly related to adverse outcomes. It is not clear whether impaired endothelial function is caused by hyperglycaemia or by other factors. Impaired endothelial function is closely associated with and may contribute to insulin resistance regardless of the presence of diabetes. Endothelial dysfunction in diabetes originates from three main sources. Hyperglycaemia and its immediate biochemical sequelae directly alter endothelial function or influence endothelial cell functioning indirectly by the synthesis of growth factors, cytokines and vasoactive agents in other cells. Finally, the components of the metabolic syndrome can impair endothelial function.
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PMID:Vascular complications in diabetes mellitus: the role of endothelial dysfunction. 1603 29

Excessive erythrocytosis results in severely increased blood viscosity, which may have significant detrimental effects on endothelial cells and, ultimately, function of the vascular endothelium. Because blood-brain barrier stability is crucial for normal physiological function, we used our previously characterized erythropoietin-overexpressing transgenic (tg6) mouse line (which has a hematocrit of 0.8-0.9) to investigate the effect of excessive erythrocytosis on vessel number, structure, and integrity in vivo. These mice have abnormally high levels of nitric oxide (NO), a potent proinflammatory molecule, suggesting altered vascular permeability and function. In this study, we observed that brain vessel density of tg6 mice was significantly reduced (16%) and vessel diameter was significantly increased (15%) compared with wild-type mice. Although no significant increases in vascular permeability under normoxic or acute hypoxic conditions (8% O2 for 4 h) were detected, electron-microscopic analysis revealed altered morphological characteristics of the tg6 endothelium. Tg6 brain vascular endothelial cells appeared to be activated, with increased luminal protrusions reminiscent of ongoing inflammatory processes. Consistent with this observation, we detected increased levels of intercellular adhesion molecule-1 and von Willebrand factor, markers of endothelial activation and damage, in brain tissue. We propose that chronic excessive erythrocytosis and sustained high hematocrit cause endothelial damage, which may, ultimately, increase susceptibility to vascular disease.
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PMID:Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain. 1625 28

Radiocontrast media can induce vascular endothelial cell apoptosis. Apoptotic damage to the vascular endothelium is an important mechanism in vascular disease. Several growth factors with anti-apoptotic effects may help protect the vascular endothelium from apoptosis. The present study evaluated whether the radiocontrast agent iopromide induces apoptosis in human umbilical vein endothelial cells and also whether angiopoietin-1 (Ang1) protects against iopromide-induced apoptosis through the p70 S6 kinase-dependent signaling pathway. Iopromide induced apoptosis in vascular endothelial cells in a dose-dependent manner. Ang1 reduced iopromide-induced apoptosis in a dose-dependent manner. Wortmannin and LY294002, phosphatidylinositol 3'-kinase inhibitors, decreased the Ang1-induced anti-apoptotic effect. Ang1 mediates the activation of mTOR/ribosomal protein p70 S6 kinase through phosphatidylinositol-3' kinase. Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. These results suggest that Ang1 may protect vascular endothelial cells from iopromide-induced apoptosis through phosphatidylinositol 3'-kinase and mTOR/S6 kinase. Pretreatment with Ang1 could help maintain normal vascular endothelial cell integrity before and during systemic radiocontrast administration.
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PMID:Angiopoietin-1 reduces iopromide-induced endothelial cell apoptosis through activation of phosphatidylinositol 3'-kinase/p70 S6 kinase. 1637 78

Coronary artery disease (CAD) and erectile dysfunction (ED) are both highly prevalent conditions that frequently coexist. Additionally, they share mutual vascular risk factors, suggesting that they are both manifestations of systemic vascular disease. The role of endothelial dysfunction in CAD is well established. Normal erectile function is primarily a vascular event that relies heavily on endothelially derived, nitric oxide-induced vasodilation. Accordingly, endothelial dysfunction appears to be a common pathological etiology and mechanism of disease progression between CAD and ED. The risk factors of diabetes mellitus, hypertension, hyperlipidemia, obesity and tobacco abuse contribute to endothelial dysfunction. This article reviews the role of vascular endothelium in health, the abnormalities resulting from vascular risk factors, and clinical trials evaluating the role of endothelial dysfunction in ED.
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PMID:Linking erectile dysfunction and coronary artery disease. 1639 38


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