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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.
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PMID:Pathogenesis of diabetic nephropathy. 1146 May 89

Vascular structure, function, and mechanics are altered in hypertension, which contributes to an important degree to complications of elevated blood pressure. Vascular hypertrophy with collagen deposition and increased stiffness is found in large arteries, whereas in small arteries, smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, particularly in milder forms of hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe hypertension. Endothelial dysfunction occurs in large or smaller vessels in a variable percentage of patients, particularly in presence of other risk factors such as diabetes, smoking, dyslipidemia, and advanced atherosclerosis. In clinical trials, 1-year treatment with angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers corrected small artery structure and endothelial dysfunction in hypertensive patients, whereas beta-adrenergic receptor blockers did not. Improved outcomes in hypertensive patients demonstrated in recent trials with some but not others of these agents could be a consequence, at least in part, of vascular protection offered by some antihypertensive agents.
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PMID:Small artery remodeling in hypertension: can it be corrected? 1146 50

Arterial remodelling plays an important part in post-angioplasty restenosis but the physiopathology of this process is not fully understood. Abundant collagen synthesis and endothelial dysfunction have been demonstrated after angioplasty, but their role in restenosis and remodelling has not been studied. The aim of this study was therefore to assess endothelial function and collagen with respect to the severity of restenosis and the type of arterial remodelling. Atherosclerosis was induced by an association of endothelial abrasion and a high cholesterol diet in the femoral arteries of 22 white New Zealand rabbits. Four weeks later, angioplasty was performed. The acetylcholine endothelium-dependant vasomotricity (expressed as % inhibition of contraction to phenylephrine), collagen and morphology were assessed 28 days after angioplasty. The change in acetylcholine endothelium-dependant vasomotricity was greater in severe restenosis (r = 0.61, p = 0.02). Endothelium-dependant relaxation was not significantly altered when remodelling was expansive and very abnormal when it was constrictive (35.5 +/- 13.0 vs 3.7 +/- 7.9%; p = 0.04). Restenosis was associated with an increase in collagen (r = 0.69, p = 0.004). The density of collagen was significantly higher in constrictive remodelling than in expansive remodelling (34.5 +/- 4.5 vs 18.2 +/- 4.7%; p = 0.03). Endothelial dysfunction and collagen accumulation are correlated with the severity of restenosis and with constrictive remodelling after angioplasty in an experimental model.
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PMID:[Mechanical and functional predictive factors for restenosis and arterial remodeling after experimental angioplasty]. 1148 Jan 59

Insulin resistance is a possible major metabolic cause of atherosclerosis. Endothelial dysfunction is commonly found in patients with insulin resistance, and primary treatment of insulin resistance with troglitazone should improve such endothelial dysfunction. Thus, the effects of troglitazone on endothelial function were investigated. Thirteen non-diabetic male subjects with hyperinsulinemic response to oral glucose load (n = 7) and normal (n = 6) subjects were investigated. Flow-mediated dilatation (FMD) of the brachial artery was examined by high resolution ultrasonography before and after the administration of troglitazone of 400 mg for 4 weeks. In insulin resistant subjects, fasting glucose (4.9+/-0.3 to 4.7+/-0.3 mmol/L, p<0.05), insulin (45+/-30 to 25+/-15 pmol/L, p<0.05) and response to oral glucose load (AUC glucose: 15.0+/-3.5 to 13.0+/-2.2 mmol x h/L, p<0.05; AUC insulin: 965+/-560 to 475+/-275 pmol x h/L, p<0.05) were significantly reduced. FMD was significantly improved in insulin resistant subjects. A significant negative correlation was observed between FMD and AUC insulin (r=-0.64, p<0.05). The present study demonstrates that FMD is impaired in insulin resistant subjects, and troglitazone improves the blunted vascular response and impaired insulin response. This finding suggests that primary treatment of insulin resistance could prevent the development of atherosclerosis by improving endothelial dysfunction.
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PMID:Troglitazone improves endothelial dysfunction in patients with insulin resistance. 1148 Apr 57

The focus of attention in preventing and treating cardiovascular (CV) disease today is shifting toward the arterial wall. Evidence has been accumulating for several years that protecting the endothelium is key to reducing CV risk. Endothelial dysfunction results in reduced compliance, or increased arterial stiffness, particularly in the smaller arteries. This abnormality is characteristic of patients with hypertension but may also be seen in normotensive patients before the appearance of clinical disease. Reduced arterial compliance is also seen in patients with diabetes and in smokers, and is part of a vicious cycle that further elevates blood pressure, aggravates atherosclerosis, and leads to increased CV risk. Although other factors are involved, the damage to the endothelium results in reduced secretion of nitric oxide, which influences smooth muscle growth, migration, and contraction, as well as influencing inflammation and clotting. Arterial compliance can be measured by several techniques, most of which are invasive or otherwise not clinically appropriate. Pulse contour analysis is a newly developed noninvasive method that allows for easy, in-office measurement of arterial elasticity to identify patients at risk for CV events before disease becomes clinically apparent. Further research is needed to confirm whether this method offers a means of improving risk stratification and therapeutic decision making.
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PMID:Arterial compliance to stratify cardiovascular risk: more precision in therapeutic decision making. 1149 6

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.
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PMID:ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans. 1149 59

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.
Atherosclerosis 2001 Sep
PMID:Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis. 1150 Jan 68

Endothelial dysfunction or activation, elicited by oxidized low-density lipoprotein (OxLDL), has been implicated in the initiation and progression of atherosclerosis. We elucidated whether tumor necrosis factor-alpha (TNF-alpha)-induced endothelial OxLDL receptor, lectin-like OxLDL receptor-1 (LOX-1), mRNA expression is modified by peroxisome proliferator-activated receptor (PPAR) activators in cultured bovine aortic endothelial cells (BAEC). We confirmed that both PPARalpha and PPARgamma were expressed in BAEC by reverse transcription-polymerase chain reaction analysis. Natural PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the thiazolidinediones, pioglitazone and troglitazone, decreased TNF-alpha-induced LOX-1 mRNA expression in BAEC. LOX-1 expression induced by phorbol 12-myristrate 13-acetate was also inhibited by 15d-PGJ(2). In contrast, PPARalpha ligands, Wy14643 and fenofibric acid, did not alter TNF-alpha-induced LOX-1 expression. TNF-alpha-induced immunohistochemical staining of LOX-1 was suppressed by 15d-PGJ(2) but not Wy14643. Taken together, PPARgamma activators inhibit TNF-alpha-induced LOX-1 expression in cultured BAEC, which may beneficially influence inflammatory responses in atherosclerosis.
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PMID:PPARgamma ligands inhibit TNF-alpha-induced LOX-1 expression in cultured endothelial cells. 1151 Oct 93

The endothelium is a major regulator of vascular tone, releasing vasoconstrictive (endothelin, cyclooxigenase-dependent factors, including prostanoids and oxygen free radicals) and vasodilating (endothelium--derived nitric oxid, endothelium--derived hyperpolarizing factor) mediators. These biologically active substances control not only the vascular tone but the vascular structure and permeability, coagulation and fibrinolysis, as well inflammatory response of the vascular wall. In endothelial dysfunction the balance in the endothelial production of vasodilating and vasoconstricting substances is altered resulting an apparent decrease in endothelium-dependent relaxations. Endothelial dysfunction is an important event in the pathogenesis of the early phase of atherosclerosis and hypertension. The testing and monitoring of endothelial dysfunction include tests of endothelium-dependent vasomotion, as well as circulating markers of endothelial damage. Further methods are needed to build up a panel of tests which measure the extent of endothelial dysfunction (= subclinical atherosclerosis), predict the subsequent risk and response to therapy.
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PMID:[Endothelial dysfunction]. 1155 60

Healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between proinflammatory and antiinflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. Endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration. The involvement of risk factors in ED is also supported by results of interventions studies that showed regression of ED with treatment of risk factors. Because risk factors are commonly accompanied by decreased bioavailability of nitric oxide, the common denominator whereby different risk factors cause ED is most probably increased oxidative stress. Endothelial dysfunction may promote atherogenesis through different mechanisms such as increased adherence of monocytes, macrophages, and enhanced permeability of the endothelial layer. Further, ED probably plays an important role in the growth of atherosclerotic lesions and in the development of thrombotic complications in late stages of the disease. Because ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and adhesion molecules). Using these tests it is possible to follow the dose response of harmful effects of risk factors, and the effects of preventive procedures on vessel wall function.
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PMID:Endothelial dysfunction in the pathogenesis of atherosclerosis. 1169 8


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