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

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI2), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin- in plasma (p), and NO and PGI2 mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years. "Placebo clamping" with NaCl infusion was performed in a subgroup of 5/51 women. During euglycaemic hyperinsulinaemic clamping, p-endothelin-1 decreased (from 3.3+/-0.2 pg/ml to 2.4+/-0.2 pg/ml; p<0.01), whereas p-neopterin (from 5.0+/-1.1 nmol/l to 6.2+/-1.4 nmol/l; p<0.001) and both intraplatelet cGMP (from 0.61+/-0.03 to 0.68+/-0.03 pmol/10(9) platelets; p<0.05) and cAMP (from 4.00+/-0.14 to 4.76+/-0.20 pmol/10(9) platelets; p<0.001) increased. Increases in cGMP (from 0.79+/-0.05 to 1.07+/-0.15 pmol/10(9) platelets; p = 0.14) and cAMP (from 4.76+/-0.15 to 5.52+/-0.36 pmol/10(9) platelets; p = 0.08) also occurred during NaCl infusion, whereas neopterin and endothelin-1 values were unchanged. In conclusion, insulin administration was associated with decreasing p-endothelin-1 levels and increasing levels of p-neopterin and intraplatelet cyclic nucleotides in accordance with vasodilatation and monocyte activation.
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PMID:Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women. 1061 52

One crucial role of endothelium is to keep the innermost surface of a blood vessel antithrombotic. However, the endothelium also expresses prothrombotic molecules in response to various stimuli. The balance between the antithrombotic and prothrombotic nature of the endothelium is lost under certain conditions. During atherosclerosis, the attachment of platelets to the vessel surface has been suggested to promote the proliferation of smooth muscle cells and intimal thickening as well as to affect the prognosis of the disease directly through myocardial infarction and stroke. Dysfunctional endothelium, which is often a result of the action of oxidized low-density lipoprotein (OxLDL), tends to be more procoagulant and adhesive to platelets. Herein, we sought the possibility that the endothelial lectin-like OxLDL receptor-1 (LOX-1) is involved in the platelet-endothelium interaction and hence directly in endothelial dysfunction. LOX-1 indeed worked as an adhesion molecule for platelets. The binding of platelets was inhibited by a phosphatidylserine-binding protein, annexin V, and enhanced by agonists for platelets. These results suggest that negative phospholipids exposed on activation on the surface of platelets are the epitopes for LOX-1. Notably, the binding of platelets to LOX-1 enhanced the release of endothelin-1 from endothelial cells, supporting the induction of endothelial dysfunction, which would, in turn, promote the atherogenic process. LOX-1 may initiate and promote atherosclerosis, binding not only OxLDL but also platelets.
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PMID:A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1. 1061 23

Endothelial dysfunction that can be detected as impaired flow-mediated dilation by ultrasonography is an early event in atherogenesis and has been demonstrated in healthy subjects with risk factors for atherosclerosis many years before the appearance of atheromatous plaques. We examined the influence of physical training on flow-mediated dilation in patients with the polymetabolic syndrome. Twenty-nine asymptomatic men aged 40 to 60 years with the polymetabolic syndrome were randomly divided between the control group and the training group, which trained 3 times a week for 12 weeks. On high-resolution ultrasound images, the diameter of the brachial artery was measured at rest, after reactive hyperemia (causing flow-mediated, endothelium-dependent dilation), and after sublingual glyceryltrinitrate (causing endothelium-independent vasodilation) in all subjects before and after the training period. The training program induced an increase of 18% in physical fitness. Flow-mediated dilation increased from 5.3+/-2.8% to 7.3+/-2.7% (P<0. 05). There was no change in body mass index, blood pressure, insulin resistance, lipids, and big endothelin-1 in either group. Flow-mediated dilation measured before training was negatively correlated with resting heart rate, waist-to-hip ratio, and insulin resistance. Resting heart rate emerged as the only independent determinant, which explained 22% of the variation in flow-mediated dilation. In conclusion, our findings suggest that a 3-month physical training program, which improved maximal exercise capacity, enhances flow-mediated dilation in patients with the polymetabolic syndrome.
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PMID:Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. 1067 Nov 87

In a previous paper we gave evidence that chronic oral defibrotide antagonizes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still capable of exerting beneficial effects on cardiovascular function once atherosclerosis is established. In fact, there was statistically significant amelioration by defibrotide infusion in the following, all of which were hampered by established atherosclerosis: in rabbit aorta relaxation to acetylcholine, prostaglandin E2, and 6-keto-prostaglandin F1alpha generation from rabbit aortas, rabbit heart left ventricular end-diastolic pressure, coronary perfusion pressure, and left ventricular developed pressure, vasopressor activity of acetylcholine and endothelin-1 on coronary perfusion pressure, and 6-keto-prostaglandin F1alpha generation from the rabbit heart. Since prostacyclin takes part in NO generation, is cellular protective, and inhibits 5-lipoxygenase product synthesis, its increase, caused by defibrotide, could explain defibrotide cardioprotective activity. Prostacyclin activity could be backed by prostaglandin E2, another cardioprotective prostaglandin.
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PMID:Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit. 1068 32

Superoxide anions (O(*-)(2)) induce oxidative stress and reduce endothelial NO availability by peroxynitrite formation. In human endothelial cells gp91(phox) was identified as the limiting subunit of the forming NAD(P)H oxidase. Because endothelin-1 (ET-1) is considered as a pro-atherosclerotic stimulus, we analyzed the effect of ET-1 on gp91(phox) expression and O(*-)(2) generation in primary cultures of human umbilical vein endothelial cells (HUVECs). The gp91(phox) mRNA expression was quantified by standard calibrated competitive reverse transcriptase-polymerase chain reaction. ET-1 induces gp91(phox) mRNA expression in HUVEC (max. after 1 h). The induction of gp91(phox) expression was dose-dependent, reaching its maximum at 10 nmol/L ET-1. The increased gp91(phox) expression is mediated by endothelial receptor type B (ET(B)). Furthermore, ET-1 augments O(*-)(2) generation in human endothelial cells as measured by coelenterazine chemiluminescence. These data support a new mechanism: how ET-1 increases oxidative stress in the vessel wall leading to endothelial dysfunction and enhanced susceptibility to atherosclerosis.
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PMID:Endothelin-1 induces NAD(P)H oxidase in human endothelial cells. 1072 Apr 82

Endothelial cells play a key role in cardiovascular homeostasis by producing several vasoactive agents, which modulate basal vascular tone and structure. Traditional risk factors of atherosclerosis contribute to endothelial dysfunction through different mechanisms such as oxidative stress, modulation of constitutive nitric oxide synthase, activation of angiotensin-converting enzyme and presumably endothelin-1. The purpose of this review was to evaluate the results of experimental and human studies on several treatment options that could improve endothelial function. However, further studies are needed to evaluate whether these different classes of drugs may improve both vascular injury and cardiovascular morbidity and mortality.
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PMID:[Therapeutic strategies in the treatment of endothelial dysfunction: facts and outlook]. 1073 78

Vein grafts are associated with adventitial remodelling which may influence innervation of the graft. Since there is also evidence that endothelin-1 (ET-1) plays a role in the adventitial remodelling process, we investigated neural distribution in porcine vein grafts 1 and 6 months after implantation, as well as the localisation of immunoreactive ET-1 and its receptors in the same tissues. Saphenous vein-carotid artery interposition grafting was performed in Landrace pigs. One and 6 months after surgery, vein grafts and ungrafted saphenous veins were excised; neural tissue and ET-1 were identified by immunocytochemistry and ET receptors were identified using in vitro autoradiography. In ungrafted saphenous veins, abundant perivascular nerves were located in the outer region of the media with only a few paravascular nerves in the adventitia. In vein grafts at 1 month after implantation, there was almost complete depletion of perivascular nerves in the media. In contrast, in the neoadventitia, there was an emphatic appearance of large paravascular nerve bundles and a marked increase in small paravascular nerves. These changes were more pronounced at 6 months after surgery, although the principal changes had occurred within 1 month. Immunoreactive ET-1 (index of ET-1 content) was associated with paravascular nerve bundles, appearing as a dark, dense ring at the perineurium. Furthermore, within the nerve bundles, positive ET-1 immunoreactivity was associated with positive alpha-actin staining, indicating that ET-1 is associated with (neural) microvessels. Also, dense 125I-labelled BQ3020 (ET(B)-selective) binding to nerve bundles was observed, indicating the presence of ET(B) receptor subtypes. ET(A) receptor subtypes were not detected in neural tissue. These data demonstrate neural reorganisation in vein grafts and indicate that ET-1 content and binding may play a role in this process. The functional consequences of these changes on neointima formation, a major cause of vein graft failure, remain to be determined.
Atherosclerosis 2000 May
PMID:Neural reorganisation in porcine vein grafts: a potential role for endothelin-1. 1078 34

Endothelial cell functions, primarily involving regulated mediator secretion or altered surface protein expression, are vital for normal homeostasis. Endothelial cells secrete the potent vasodilator and anti-platelet agent prostacyclin and nitric oxide, and also the potent vasoconstrictor peptide endothelin-1; they control the selective adhesion and emigration of leukocytes from the bloodstream; and they are the source of circulating von Willebrand factor, tissue plasminogen activator and type 1 plasminogen activator inhibitor. The properties of healthy endothelium ensure that an antithrombotic and anticoagulant balance is maintained in the bloodstream, and provide a tonic vasodilator action that controls blood flow and pressure on a minute-to-minute basis. Disturbances of normal endothelial function are strongly implicated in the pathogenesis of atherosclerosis and autoimmune vasculitic diseases including lupus.
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PMID:Normal endothelial cell function. 1080 85

The potent vasoconstrictor peptide endothelin-1 (ET-1) has been implicated in the pathophysiology of atherosclerosis and its complications. Since inflammation of the vessel wall is a hallmark of atherosclerosis, the purpose of the present study was to investigate the influence of ET-1 on cytokine production in human vascular smooth muscle cells (SMC) as a marker of inflammatory cell activation. ET-1 (100 pM - 1 microM) stimulated interleukin-6 (IL-6) secretion from human vascular SMC in a concentration-dependent manner. The ET-A-receptor antagonist BQ-123 (10 microM), but not the ET-B-receptor antagonist BQ-788, inhibited IL-6 release. ET-1 also transiently increased IL-6 mRNA compatible with regulation of IL-6 release at the pretranslational level. Electrophoretic mobility shift assays demonstrated time- and concentration-dependent activation of the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in ET-1-stimulated human vascular SMC. A decoy oligodeoxynucleotide bearing the NF-kappaB binding site inhibited ET-1-stimulated IL-6 release to a great extent suggesting that this transcription factor plays a key role for cytokine production elicited by ET-1. Moreover, the antioxidant pyrrolidine dithiocarbamate (10 microM) inhibited ET-1-induced IL-6 release indicating involvement of reactive oxygen species in ET-1 signaling. ET-1-stimulated IL-6 secretion was also suppressed by diphenylene iodonium (40 microM), an inhibitor of flavon-containing enzymes such as NADH/NADPH oxidase. The results demonstrate the ability of ET-1 to induce an inflammatory response in human vascular SMC. These observations may contribute to a better understanding of the role of ET-1 in inflammatory activation of the vessel wall during atherogenesis.
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PMID:Endothelin-1 induces interleukin-6 release via activation of the transcription factor NF-kappaB in human vascular smooth muscle cells. 1082 1

Increased evidence has shown that endothelin-1 (ET-1) derived from the arterial cells is involved in the development of atherosclerosis. ET-1 and ET receptors are upregulated in both human and experimental animal atherosclerotic lesions. Plasma ET-1 levels are significantly elevated in hypercholestolemic subjects and cholesterol-fed animals. We hypothesized that plasma lipoproteins such as LDL and HDL retained in the arterial wall can affect ET-1 production and secretion, thereby sustaining vascular functions. Using a two-chamber culture system, we have demonstrated that endothelial cells (ECs) show a polar secretion of ET-1; the majority of ET-1 are secreted toward the basal side of the vessels. Furthermore, we found that LDL enhances whereas HDL inhibits the ET-1 secretion from ECs in a polarized pattern. In order to demonstrate ET receptor distribution in the lesion, we recently studied both human and apoE-KO mice. Our study showed that there is an increased expression of ETB receptors in foamy macrophages in the lesions. More importantly, medial smooth muscle cells (SMCs) beneath the foam cell lesions exhibited a higher intensity of ETB receptor immunoreactivity than those located in foam cell-free areas. In such an area, ET-1 immunoreactivity is also increased. These results suggest that accumulation of foamy macrophages may modulate the shift of ET receptor subtypes from ETA to ETB in SMCs and an enhanced ET system mediated by ETB receptors may play a pivotal role in the progression of atherosclerosis. This notion has been further supported by a recent finding that administration of ET receptor antagonists resulted in a significant reduction of atherosclerosis in apoE-KO mice.
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PMID:Role of endothelin-1 in atherosclerosis. 1086 28


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