Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is characterized by hypertrophy of the vascular media, intimal thickening and lipid-containing plaques. Atherosclerosis is a progressive systemic vascular disease which leads to impaired tissue perfusion due to vascular obstruction. In advanced stages it is often complicated by thrombosis. Recent research demonstrates that atherosclerosis is also a functional disease. In atherosclerosis and hypercholesterolemia, normal vasodilatation is impaired due to endothelial dysfunction. In addition, the ability of the vessel wall to reject adhering and aggregating platelets is deteriorated. Endothelial dysfunction in atherosclerosis is characterized by impaired formation of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF). NO is continuously formed in the vascular endothelium and promotes tissue perfusion by relaxation of vascular smooth muscle. Endogenously formed NO may also protect against foam cell formation and media hypertrophy, i.e. against the structural component of atherosclerosis. In patients with ischaemic heart disease, the endothelial dysfunction leads to decreased ability to dilate the coronary vessels in response to several forms of physiological stimuli. Endothelial dysfunction in atherosclerosis is reversed by lipid-lowering therapeutic interventions.
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PMID:Nitric oxide (NO) in the cardiovascular system: role in atherosclerosis and hypercholesterolemia. 786 90

Diabetes mellitus is a major cause of ischemic coronary artery disease. Endothelial dysfunction is implicated in the pathogenesis of diabetic vascular disease. To examine coronary blood flow (CBF) regulation with endothelium-derived nitric oxide (EDNO) in the diabetic state, we compared the effects of both acetylcholine (ACh) and adenosine (Ado) on left circumflex coronary artery (LCX) blood flow in 12 vehicle-treated and 21 dogs made diabetic with alloxan anesthetized with pentobarbital. All dogs were pretreated with aspirin to inhibit endogenous prostaglandins. None of the hemodynamic parameters were significantly different in the two groups. The percent change in coronary vascular resistance (CVR) after ACh (100 ng/kg) infusion was significantly attenuated in diabetic dogs (-56.5 +/- 1.4%) as compared with vehicle-treated dogs (-64.5 +/- 1.2%) (p < 0.01), whereas the effect of Ado (1 microgram/kg) was not different between the two groups (-71.1 +/- 1.5% in vehicle, -67.0 +/- 1.3% in diabetes). After infusion of incremental doses of NG-nitro-L-arginine methyl ester (L-NAME) 10(-5)-10(-3)M, the effect of ACh was progressively inhibited in both groups and was different no longer between the two groups after the maximal dose. L-Arginine (L-ARG), but not D-ARG, significantly restored the effect of ACh in diabetic dogs but did not affect vehicle-treated dogs. The effect of Ado did not change after L- and D-ARG administration. Cu, Zn-superoxide dismutase (Cu, Zn-SOD) had no effect on any of the effects of ACh and Ado in diabetic dogs. Regulation of CBF with EDNO is impaired in dogs with alloxan-induced diabetes, and this impairment is partially restored by L-ARG.
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PMID:Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in dogs with alloxan-induced diabetes. 879 37

Recent insights into the pathogenesis of vascular disease have opened up a new frontier that has implications for future therapies. The vasculature has been redefined as a vital organ that can regulate its own tone and structure via numerous cellular mechanisms. The endothelium plays the role of gatekeeper in this process, sensing and responding to stimuli and activating various vasoactive systems that function as mediators. Locally generated vasoactive substances such as angiotensin II and nitric oxide appear to be important determinants of vessel function and structure. Vasoactive substances generated within the endothelium influence cell proliferation and cell death in a complex interplay that, when disturbed, can result in structural alteration known as vascular remodeling. Normal vascular homeostasis is maintained by a balance between vasoconstrictors such as angiotensin II and vasodilators such as nitric oxide. Endothelial dysfunction involves an imbalance between vasoactive substances such that perturbations in the regulation of tone, hemostasis, and vessel structure result in the development of cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure.
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PMID:Endothelial function as a determinant of vascular function and structure: a new therapeutic target. 912 14

Endothelial dysfunction has an important role to play in the pathophysiology of human vascular disease. The maintenance of barrier function is critical to the role of vascular endothelium in cardiovascular haemostasis and this function can be compromised by inflammatory mediators, cytokines or oxidants. Under conditions of oxidative stress a variety of reactive oxygen species (ROS) may be generated, which increase the permeability of the endothelial monolayer to fluid, macromolecules and inflammatory cells. The endothelium-derived nitric oxide radical (NO), whose physiological actions include effects on vascular smooth muscle, is normally inactivated by the superoxide radical anion. While large amounts of NO have cytotoxic potential, it is now becoming clear that combinations of NO with ROS can produce either cytotoxic or cytoprotective effects, depending on the relative amounts of each which are present in the target cell or its environment at a particular time. The contribution of NO to oxidant-mediated endothelial barrier dysfunction can be assessed in vitro in endothelial monolayers grown on porous membrane supports. In this model, using hydrogen peroxide (H2O2) as the oxidant, H2O2-induced losses of barrier function can be enhanced or partially offset by NO donor drugs, depending on the concentration of NO donor used. Furthermore, the injurious or cytoprotective effects of these agents appear to be determined by the quantity of NO generated. Since NO is administered clinically by inhalation in conditions such as pulmonary hypertension or the adult respiratory distress syndrome, which are themselves associated with generation of ROS, it is likely that low concentrations of NO may protect the pulmonary vascular endothelium while high concentrations might be expected to combine with ROS to yield intermediates capable of causing further endothelial injury or loss of barrier function.
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PMID:Endothelial barrier dysfunction and oxidative stress: roles for nitric oxide? 912 51

Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure (CRF). Endothelial dysfunction is a key early event in atherogenesis. The aim of this study was to assess the effect of CRF on endothelial function using physiological and biochemical measures. To focus on the effect of CRF itself, 23 children (matched with 23 controls for age and vessel diameter) were selected because they were normotensive, had normal total cholesterol (TC) levels, and were not on vasoactive drugs. Their mean (range) age was 12.0 (7.8 to 17.0) years; GFR 17.5 (8.8 to 34.5) ml/min/1.73 m2. The physiology of endothelial function in the brachial artery was assessed using high resolution ultrasound by measuring its diameter at rest, during reactive hyperemia (endothelium dependent dilation) and after sublingual glyceryl trinitrate (GTN; endothelium independent dilation). Nitric oxide (NO) metabolites and endogenous NO synthetase (eNOS) inhibitors were measured as an assessment of endothelial metabolism. Brachial artery dilation to flow [FMD, mean (SEM)%] was reduced in CRF to 4.9 (0.6) and controls 8.6 (0.6), P < 0.0001. In contrast, the response to GTN was similar in both groups: CRF 25.1 (1.6), controls 23.3 (1.2), P = 0.31. There was no difference in TC, low density lipoprotein (LDL) or high density lipoprotein (HDL) between the patients and the controls. Triglycerides (TG) were higher in the patients but within the normal range. Antibodies against oxidized LDL (ox-LDL) were high in CRF. Endogenous NOS inhibitors were high in CRF, and intermediate NO metabolites were low. There was no correlation between FMD of the brachial artery and lipid subfractions, or with NO metabolites or eNOS inhibitors. Endothelium dependent dilation of the brachial artery is impaired in children with CRF who do not have co-existing risk factors for atherosclerosis. This may represent early evidence of atherogenic vascular disease.
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PMID:Physiology and biochemistry of endothelial function in children with chronic renal failure. 926 3

Elevated plasma levels of homocysteine and disulfide adducts of homocysteine (collectively termed "homocyst(e)ine") are associated with increased risk of thrombotic and atherosclerotic vascular disease. It is still not evident, however, whether moderately elevated plasma homocyst(e)ine concentration per se is a cause, or rather just a marker for an associated condition that may predispose to development of vascular disease or its complications. This distinction has important clinical consequences, since dietary intervention to lower plasma homocyst(e)ine has been proposed as a global strategy to decrease the prevalence of vascular disease. Studies of cultured cells in vitro have led to the hypothesis that homocysteine may predispose to vascular disease by altering the normally antithrombotic and vasoprotective phenotype of vascular endothelium, perhaps through a mechanism that involves generation of peroxides and other reactive oxygen species. Recent findings in animal and human models of moderate hyperhomocyst(e)inemia provide support for some aspects of this hypothesis. Endothelial dysfunction in hyperhomocyst(e)inemia may contribute to development of atherosclerosis and predispose to complications such as thrombosis and vasospasm. Important questions to be addressed in future investigations include the relative importance of homocysteine versus associated conditions (such as folate deficiency) in the etiology of vascular dysfunction, the role of homocysteine-induced oxidant stress, and the potential benefits of lowering plasma homocyst(e)ine levels through dietary supplementation with B vitamins.
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PMID:Homocysteine and vascular dysfunction. 932 62

Growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) exert important effects on endothelial cells in vitro and in vivo. This article reviews the effect of these two growth factors on endothelial dysfunction in various animal models of vascular disease: (1) collateral circulation supplying an ischemic territory, (2) balloon injury, and (3) diet-induced experimental atherosclerosis. Endothelial dysfunction may limit the beneficial effects of collateral vessels on tissue perfusion. Administration of VEGF or basic FGF (bFGF) augments collateral development in different models of hindlimb ischemia by enhancing neovascularity and by facilitating the recovery of endothelial function in the collateral circulation. Similarly, studies performed after balloon angioplasty have demonstrated abnormal responses of previously dilated sites to endothelium-dependent agonists. Administration of VEGF or bFGF increases endothelial regrowth and normalizes endothelium-dependent responses after experimental angioplasty. Finally, endothelium-dependent relaxation is impaired in diet-induced experimental atherosclerosis. It was recently demonstrated that hypercholesterolemic rabbits treated with bFGF had significantly better endothelium-dependent responses than those not treated with bFGF. These results show that in vivo administration of the endothelial cell growth factors VEGF and bFGF leads to significant improvement in endothelium-dependent responses and supports the concept of using these growth factors as a new therapeutic strategy for patients with vascular diseases.
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PMID:Growth factors as a potential new treatment for ischemic heart disease. 942 53

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.
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PMID:Measures of endothelial function as an endpoint in hypertension? 949 29

Abnormalities in vascular endothelial function, which occur early in atherosclerosis, may play an etiologic role in the development of the disease or represent a marker for the extent of atherosclerosis. Endothelial dysfunction, usually characterized by demonstration of decreased endothelium-dependent vasorelaxation, may be a sensitive and specific method to detect vascular disease in its earliest stages. In this context, separation of abnormalities in receptor-mediated and flow-mediated endothelium-dependent vasodilatory responses may allow for the most accurate characterization of endothelial dysfunction. In 35 patients undergoing routine annual cardiac catheterization after heart transplantation, changes in epicardial lumen area and coronary blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously using an intravascular ultrasound (IVUS) catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed for distinction between receptor-mediated and flow-mediated endothelium-dependent vascular responses. Peak flow with the endothelium-independent resistance vessel dilator adenosine occurred at 18+/-2 sec; the maximal lumen area response occurred later, at 43+/-11 sec (P < 0.001). Acetylcholine, an endothelium-dependent small- and large-vessel vasodilator, caused an immediate increase in both flow and lumen area, but a second peak of dilation was observed, and maximal area occurred 46 sec after maximal flow (54+/-14 vs. 100+/-26 sec, P < 0.001). Simultaneous IVUS and Doppler flow measurements after infusion of vasoactive agents allows for distinction between and evaluation of the relative contribution of agonist-mediated and flow-mediated responses, which may offer important and unique insights into coronary endothelial function.
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PMID:Simultaneous intracoronary ultrasound and Doppler flow studies distinguish flow-mediated from receptor-mediated endothelial responses. 1034 24

Atherosclerotic macrovascular disease is the leading cause of both morbidity and mortality in non-insulin dependent diabetes mellitus. Endothelial dysfunction is a key, early and potentially reversible event in pathogenesis of atherosclerosis. Its occurrence in non-insulin dependent diabetes mellitus is well supported by both in-vitro and in-vivo studies. Non-insulin dependent diabetes mellitus results in diverse abnormalities of lipid and lipoprotein metabolism, in particular hypertriglyceridaemia, low levels of high density lipoprotein and abnormalities of post-prandial lipaemia. A variety of studies demonstrate the presence of enhanced oxidative stress in non-insulin dependent diabetes mellitus, with recent data implying an association between oxidative stress, post-prandial lipaemia and endothelial dysfunction in non-diabetic subjects. In this article based on in-vitro and human studies, we develop the hypothesis that endothelial dysfunction in non-insulin dependent diabetes mellitus is the consequence of the diabetic dyslipidaemia, in particular post-prandial lipaemia, and of oxidative stress on the action of nitric oxide. The practical applications of this theory provide potential therapeutic options which may reduce the risk of vascular disease in non-insulin dependent diabetes mellitus.
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PMID:Diabetic dyslipidaemia and coronary heart disease: new perspectives. 1055


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