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

Vascular responses to intraluminal and abluminal activation of human platelets were examined in carotid arteries from normal and atherosclerotic rabbits. The carotid artery was perfused in vitro, platelets were activated with thrombin (0.1 unit/ml), and changes in diameter were measured. In vessels from normal animals, intraluminal activation of platelets produced dilatation of preconstricted arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5) M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist. Abluminal activation of platelets produced modest constriction in quiescent arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP produced pronounced dilatation of preconstricted arteries. In vessels from atherosclerotic animals, endothelium-dependent dilatation to intraluminal activation of platelets and to ADP was impaired and dilator responses to sodium nitroprusside were normal. These experiments indicate that 1) intraluminal activation of human platelets produces endothelium-dependent dilatation in perfused carotid arteries, whereas abluminal activation of human platelets produces vasoconstriction, which is mediated primarily by serotonin, and 2) atherosclerosis markedly impairs vasodilator responses to activation of human platelets, probably because vasodilatation to ADP released from platelets is impaired.
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PMID:Effect of atherosclerosis on responses of the perfused rabbit carotid artery to human platelets. 139 May 92

We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.
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PMID:Abnormalities in platelets and vascular endothelial cells induced by glycated lipoproteins. 139 75

Cadaveric aortic intimas with uncomplicated atherosclerosis were examined to determine the distribution and polypeptide chain composition of fibrinogen-related protein. Immunohistochemical staining showed deposits rich in fibrinopeptides A and B. The deposits were usually disseminated throughout intimas of moderate thickness < 0.7 mm, but were distributed focally in elongate patches bounded both lumenally and medially by deposit-free tissue in thick atheromas. Saline extracts generally showed undegraded monomers and dimers by electrophoresis. The residual protein contained A alpha and gamma-chains that were cross-linked predominantly (>80%) into unresolved high M(r) (>200 kd) derivatives, whereas B beta-chains were left non-cross-linked, as occurs in late stages of cross-linking by transglutaminases. The resolved components had electrophoretic mobilities corresponding to characteristic products of both factor XIIIa and tissue-transglutaminase. A greater incorporation of alpha- rather than gamma-chains into cross-linked products implicated tissue-transglutaminase as contributing heavily. By contrast, vascular graft pseudo-intimas and a cadaveric clot were rich in degraded fibrin devoid of fibrinopeptide A, and cross-linked in patterns typical of XIIIa with gamma 2 dimers constituting the principal product. The findings indicate that the fibrinogen in the aortic intima is comparatively well protected from thrombin and plasmin, and that much of it is deposited through direct cross-linking by tissue-transglutaminase without being converted to fibrin.
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PMID:Immunoelectrophoretic and immunohistochemical characterizations of fibrinogen derivatives in atherosclerotic aortic intimas and vascular prosthesis pseudo-intimas. 141 80

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.
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PMID:Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery. 145 16

In the present study performed on rats, we investigated the influence of an in vivo acute iron load on several platelet parameters and their modification after vitamin E supplementation. Iron load was achieved by injecting iron dextran corresponding to 0.1 mg Fe3+ per kg in the gluteus muscles. Control rats were injected with an equal amount of a dextran solution. Analyses were performed 18 h after injection. By comparison with controls, in iron-injected animals, we found significant increases of: (1) serum total iron (by 110%); (2) aggregation of isolated platelets induced by low concentration of thrombin and ADP (by 350% and 120%, respectively); (3) thrombin-induced endogenous serotonin secretion (by 94%). We also studied the mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids. The results indicated that the thrombin-stimulated release of arachidonate and formation of cyclooxygenase and lipoxygenase products (particularly thromboxane B2), were significantly increased. We also found in plasma an increase (by 67%) of malondialdehyde (MDA) as well as a decrease of vitamin E (by 60%). When vitamin E was injected the day before iron injection, platelet hyperactivity and thromboxane biosynthesis were reduced as well as the plasma MDA concentration. Consequently, given the key role of calcium flux in the activation processes in platelets, we also investigated the thrombin-induced Ca2+ uptake by means of radiocalcium. We found that in platelets from iron-treated rats the Ca2+ uptake amounted to 3670 +/- 201 pmol/10(9) platelets (plt) and was significantly different from controls (1680 +/- 192 pmol/10(9) plt, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Oct
PMID:Effect of vitamin E on acute iron load-potentiated aggregation, secretion, calcium uptake and thromboxane biosynthesis in rat platelets. 146 49

This study was conducted to investigate acute effects of smoking on platelet function, endothelial cells and plasma lipids and to follow these parameters after Aspirin ingestion. Twelve fasting smokers each inhaled the smoke of one cigarette. Blood was drawn before and 10 min after smoking. Plasma nicotine, measured by gas chromatography, increased from 13.48 before smoking to 78.41 nM after smoking. Platelet aggregation to thrombin and ADP increased significantly (P less than 0.001). The platelet aggregate ratio decreased from 0.95 to 0.75 (P less than 0.005). Plasma beta-thromboglobulin also increased in post-smoking samples as measured using radioimmunoassay. 'Circulating endothelial cells' increased significantly after smoking (P less than 0.005). Triglycerides decreased (P less than 0.005) in plasma and in the VLDL fraction (P less than 0.05). Both post-smoking plasma free fatty acids and free glycerol increased, respectively, as compared with respective values. Lipase activity ascribable to lipoprotein lipase and hepatic lipase, absent in pre-smoking plasma samples, could be detected in post-smoking plasma without heparin injection. At least 1 week later, the subjects returned to follow an identical protocol except that they had ingested Aspirin (650 mg) 10-14 h before blood sampling. The same parameters were measured before and after smoking the same cigarette. Except for plasma nicotine, all the smoking-induced changes were abolished by ingestion of Aspirin. The results of this study indicate an interrelationship between platelet hyperactivity, endothelial injury and plasma lipids. They also demonstrate an inhibition of the major smoking-induced changes by Aspirin in the presence of high plasma nicotine levels. It is concluded that Aspirin may offset several of the deleterious acute effects of smoking. However, our conclusions cannot be, in any way, extended for long-term effects of both smoking and Aspirin treatment. Based on these data, it is suggested that there may be some links between platelet hyperactivity, endothelium injury and plasma lipids.
Atherosclerosis 1992 Apr
PMID:Acute influence of smoking on platelet behaviour, endothelium and plasma lipids and normalization by aspirin. 146 56

Endothelin is a newly discovered potent vasoconstrictive polypeptide released by endothelial cells in response to various stimuli, including vasoactive peptides such as angiotensin II, adrenaline and vasopressin, and thrombocyte products like transforming beta growth factor and thrombin. Endothelin is believed to exert its main effects locally, in a paracrine or autocrine way. In vascular tissue, endothelin induces longlasting contraction of smooth muscle cells, leading to decreased blood flow, especially in the coronary and renal circulation, together with an increase in systemic blood pressure. It acts also mitogenically in vascular smooth muscle cells. Endothelin stimulates release of aldosterone and catecholamines in non-vascular tissue, and inhibits release of renin. A physiological function of endothelin may be to modulate vascular tone, and increased levels of circulating endothelin are seen after the "cold pressor test". Moreover, plasma endothelin concentration is elevated during acute myocardial infarction, in acute renal failure, in patients with hypertension, and during cardiogenic chock. What role endothelin plays in the development of these conditions, and in other disorders such as vascular spasm and atherosclerosis is uncertain.
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PMID:[The endothelial cell as an endocrine organ--endothelin]. 155 33

Leukocyte adhesion and other injury parameters have been studied in the aortic endothelium of Sprague-Dawley rats in two situations: (1) spontaneous pathology in conventional rats with antibodies to Mycoplasma pulmonis and/or Kilham or Sendai viruses, and (2) intravascular coagulation by thrombin administration in SPF rats. Adhesion (esterase (+) leukocytes/mm2) in SPF rats was 8 +/- 5 (n = 12). Adhesion in 38% of the conventional rats was 54 +/- 27 (n = 8), half of them being non-analyzed and the rest having antibodies to M. pulmonis and/or Kilham rat virus. In 19 rats with antibodies to M. pulmonis and/or Kilham or Sendai viruses, AgNO3 and hematoxylin staining of the aortic endothelium showed an increase in leukocyte adhesion, and the presence of argyrophilic cells, stigmata and granularity--severe endothelial lesions being observed in some cases. Adhesion in rats after 0.25, 1, 3 and 6 h of thrombin administration (30 units/100 g) was not different from controls. Adhesion after 24 h was 108 +/- 53 (n = 10) and 60 +/- 59 (n = 10), and 22 +/- 20 (n = 10) in rats treated with thrombin plus heparin or hirudin, respectively. Thrombin produced endothelial lesions at all times studied, and these included membrane blebs, platelet and erythrocyte adhesion and alterations in the pattern of endothelial esterase activity.
Atherosclerosis 1992 Apr
PMID:Effect of spontaneous pathology and thrombin on leukocyte adhesion to rat aortic endothelium. 159 Aug 26

Elevation of cytosolic ionized calcium plays a critical role in human platelet activation. We have evaluated three well-characterized calcium antagonists for their ability to prevent thrombin-induced calcium mobilization in Fura 2 AM-loaded platelets and also their ability to inhibit platelet-vessel wall interactions. Thrombin (0.2 U/ml) caused significant elevation of cytosolic calcium (basal 84 +/- 18, activated 546 +/- 76 nM; n = 3). Verapamil, diltiazem, and nifedipine (100 microM) did not exert any inhibitory effect on thrombin-mediated calcium elevation. Untreated platelets perfused through a Baumgartner chamber containing a rabbit aorta preparation reacted with exposed and denuded subendothelium. The percentage of the total area covered by control platelet thrombi was 39.6 +/- 3.4. Diltiazem and Nifedipine significantly reduced the percentage of area covered by platelet thrombi, but the drugs were not as effective as aspirin (8.2 +/- 1.4). Calcium antagonists studied did not inhibit thrombin-stimulated elevation of cytosolic calcium in blood platelets. Although these drugs have been shown to prevent in vitro platelet aggregation and offer some protection against risks for atherosclerosis and thrombosis, they failed to significantly inhibit platelet-vessel wall interactions leading to formation of spread platelets and aggregates.
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PMID:Influence of calcium antagonists on thrombin-induced calcium mobilization and platelet-vessel wall interactions. 162 53

Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent.
Atherosclerosis 1992 Jul
PMID:Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells. 164 92


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