Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether thrombin directly modifies mobility of vascular smooth muscle cells (SMC), in Transwell systems (modified Boyden chambers), we exposed SMC to alpha-thrombin. In concentrations as low as 1 NIH U/ml, thrombin induced migration as well as proliferation of SMC. Inhibition of protein synthesis by cycloheximide (2 micrograms/ml) obviated thrombin's chemotactic effect. Neither gamma-thrombin nor D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK)-inactivated alpha-thrombin (both used as controls) exerted a chemotactic effect. Concomitant hirudin or antithrombin III plus heparin inhibited chemotaxis by thrombin when added up to 2 h after addition of thrombin. alpha-Thrombin increased SMC synthesis of urokinase receptor (uPAR) and its cell surface expression as shown by metabolic labeling and immunoprecipitation as well as by flow cytometry. Thus alpha-thrombin, in concentrations thought to be present in vivo at sites of vascular injury, can stimulate not only proliferation but also migration of vascular SMC though a mechanism(s) possibly involving synthesis of uPAR, which is known to influence migration in diverse types of cells. Accordingly, both proliferation and migration dependent on thrombin may accelerate atherosclerosis, restenosis, or both after interventions such as angioplasty.
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PMID:Vascular smooth muscle cell migration mediated by thrombin and urokinase receptor. 776 12

The relationship of ischaemic heart disease (IHD) to seasonal and latitude variation has prompted speculation that exposure to the ultraviolet component of solar radiation may reduce IHD risk. This hypothesis was partially tested by exposing 14 post-myocardial infarction patients to a 6 week course of artificial whole-body ultraviolet radiation (UVR). Serum lipoprotein and plasma coagulation factor concentrations were measured before and after the course of UVR. Results were compared with similar measurements from a placebo-controlled group of 13 post-myocardial patients. Despite a more than two-fold rise in mean serum 25-OHD, serum lipoprotein and plasma fibrinogen, antithrombin III and plasminogen concentrations did not change significantly in the UVR group. Significant but minor change in prothrombin time and thrombin time in the placebo group appear unlikely to be of biological significance. Seasonal and latitude variation in these IHD risk factors appear unrelated to corresponding variation in solar UVR exposure.
Atherosclerosis 1994 May
PMID:Artificial ultraviolet whole-body radiation does not modify serum lipoprotein, plasma fibrinogen, plasminogen or antithrombin III concentrations in post-myocardial infarction patients. 794 60

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.
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PMID:Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. 799 2

Sixteen patients with lower limb atherosclerosis (LLAS) stage II-III received autotransfusions of blood irradiated by ultraviolet light. Vascular wall antithrombogenic properties assessed before the treatment in the patients and controls were found deteriorated in LLAS subjects. The cuff test did not affect the antithrombogenic characteristics. The course of autotransfusions produced a clinical improvement and strengthening of the antithrombogenic properties. The cuff test demonstrated a significant decline in platelet aggregation in response to ADP, thrombin, collagen, ristomycin, arachidonic acid; of platelet factor 4, thromboxane B2, beta-thromboglobulin. Concentrations of antithrombin III, plasminogen, prostacyclin rose. The autotransfusions were made on "Izolda" device MD-73 (1 ml of blood per 1 kg b. mass). Irradiation dose 750 J/m2, wave length 254 nm. Platelet aggregation was studied according to Born technique in O'Brien modification. Thromboxane B2, 6-keto-PGF1 alpha, beta-thromboglobulin and TF 4 were measured by radioimmunoassay, antithrombin III and plasminogen by chromogenic substrates.
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PMID:[The antithrombogenic properties of the vascular wall and platelet aggregation in patients with atherosclerosis of the arteries of the lower extremities following a course of treatment with UV-irradiated autologous blood transfusion]. 802 Jul 15

Plasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean F1 + 2 (0.63 vs 1.62 nmol/l, p < 0.0001) and TAT levels (1.65 vs 2.23 micrograms/l, p < 0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients' age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 micrograms/l; p = 0.06). Both F1 + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (F1 + 2: 1.76 vs 1.36 nmol/l, TAT: 2.35 vs 2.00 micrograms/l; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between F1 + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.
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PMID:Prothrombin activation fragment 1 + 2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. 811 78

This study of 49 patients with spontaneous venous and arterial thrombosis identified 27 with hypercoagulable states: 13 had only venous thrombosis (VT), six had episodes of VT followed by arterial thrombosis (AT) and eight had AT only. All 27 patients were less than 42 years of age; 22 had specific natural anticoagulant or fibrinolytic deficiencies: antithrombin III (nine patients), protein C (eight patients), protein S (three patients), heparin cofactor II (two patients), tissue plasminogen activator release (one patient) and mixed antithrombin III and protein S (one patient). The remaining five patients had recurrent thrombotic events associated with resistance to heparin anticoagulation, but no established laboratory diagnosis. Clotting complications included recurrent VT, pulmonary embolism, multiple failed arterial procedures and lower extremity amputation. The remaining 22 patients (mean age of 53 years, range of 46 to 63 years), 12 with VT and ten with AT, did not have laboratory evidence of hypercoagulability and none had recurrent vascular occlusions. All these patients were successfully treated by conventional therapy without any additional thrombotic events during the follow-up period. Young adults with spontaneous thrombotic events should be screened for possible hypercoagulable states. Additionally, these young patients need further evaluation and treatment of cardiovascular risk factors. Those with premature atherosclerosis have an especially poor prognosis despite surgical intervention and anticoagulant therapy.
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PMID:Hypercoagulable states as an evolving risk for spontaneous venous and arterial thrombosis. 792 7

Thrombin, the final product of blood coagulation cascade, shows several effect on the vessel-wall cells. However the effects may be regulated by several thrombin receptors on the endothelium. They include thrombomodulin (TM), protease-Nexin, heparin-like molecule-antithrombin III complex. These binding sites do not transduce the signal of thrombin. Especially TM converts thrombin from a procoagulant protease to an anticoagulant. Recently new thrombin receptor was identified on the endothelium and platelets. Through this receptor, thrombin induces activations both on platelet end-endothelium. In brief platelets aggregate and release several factors including serotonin, PDGF, platelet factor4, beta-thromboglobulin on the stimulation by thrombin. The endothelium release t-PA inhibitor; PAI-1, prostacyclin and endothelin. Thus the activations of these cells by thrombin is a key events in hemostasis, wound healing, inflammation, atherosclerosis and restenosis of coronary artery after PTCA.
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PMID:[Regulation of the endothelial function by thrombomodulin and/or thrombin receptor]. 815 41

The endothelial surface plays an important role in the pathogenesis of atherosclerosis and the regulation of coagulation. It has become increasingly clear that while perturbed endothelial cells generate procoagulant activity, under normal conditions they possess multiple antithrombotic and anticoagulant mechanisms, including generation of prostacyclin and plasminogen activators and synthesis of thrombomodulin as a cell surface cofactor for thrombin-catalyzed activation of protein C. In addition, anticoagulantly active heparan sulfate proteoglycans, including heparin-like molecules are apparently present on the vascular surface. Previous studies showed that homocysteine, a thromboatherogenic and atherogenic agent, inhibits an endothelial thrombomodulin-protein C anticoagulant pathway. We examined whether homocysteine might affect another endothelial anticoagulant mechanism; i.e., heparin-like glycosaminoglycan-antithrombin III interactions. Incubations of cultured endothelial cells with homocysteine reduced the amount of antithrombin III bound to the cell surface in a dose- and time-dependent fashion. In contrast with a marked reduction in the maximal antithrombin III binding capacity, the radioactivity of [35S] sulfate incorporated into heparan sulfate on the cell surface was minimally reduced. Although neither net negative charge nor proportion in total glycosaminoglycans of cell surface heparan sulfate was altered by homocysteine treatment, a substantial reduction in antithrombin III binding capacity of heparan sulfate isolated from homocysteine-treated endothelial cells was found using both affinity chromatography and dot blot assay techniques. The antithrombin III binding activity of endothelial cells decreased after preincubation with homocysteine, cysteine, or 2-mercaptoethanol, containing a sulfhydryl group; no reduction in binding activity was observed after preincubation with methionine, alanine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Heparan sulfate proteoglycan of endothelial cells: homocysteine suppresses anticoagulant active heparan sulfate in cultured endothelial cells]. 817 41

Immunohistochemical studies of human atherosclerotic lesions have demonstrated the occurrence of fibrin deposition and its degradation in the arterial wall. We studied fibrinogen, the generation of thrombin, and the degradation of fibrin in 40 patients with stable peripheral arterial occlusive disease of varying severity, as assessed by the ankle/brachial pressure index and duplex ultrasonography and/or angiography. Circulating fibrinogen (functional and immunological), fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer were measured. The severity of atherosclerosis was associated with both fibrinogen (both functional and immunological) and D-dimer (r = .57, P < .0002, and r = .57, P < .0001, respectively). Fibrinogen and D-dimer showed a significant positive correlation (r = .50, P < .001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antithrombin III complex. As a sign of coagulation activation and fibrinolysis, we found that thrombin-antithrombin III complex and the degradation of cross-linked fibrin were progressively associated with the extent of vascular disease. The plasmin-mediated fibrin breakdown contributed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations between fibrinogen/D-dimer and the severity of atherosclerosis support previous pathological studies and imply that local degradation of cross-linked fibrin is involved in the progression of atherosclerosis.
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PMID:Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. 824 Oct 93

The relation of hemostatic factor levels to the occurrence of cardiovascular disease is incompletely established. The Atherosclerosis Risk in Communities Study measured fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C, activated partial thromboplastin time, and other cardiovascular risk factors in nearly 15,000 men and women aged 45 to 64. This analysis assessed the relations of these hemostatic factors with prevalent cardiovascular disease and asymptomatic carotid artery intimal-medial thickness measured by B-mode ultrasound. Compared with participants without cardiovascular disease, those with cardiovascular disease had higher levels of fibrinogen, factor VIII, and von Willebrand factor in both sexes. The other hemostatic factors were less consistently associated with prevalent cardiovascular disease. Only fibrinogen was associated with carotid intimal-medial thickness. Adjusted for age, race, and field center, the odds ratio for carotid wall thickness in the 90th percentile or greater, compared with < 50th percentile, for each SD higher fibrinogen concentration (65 mg/dL) was 1.42 (95% confidence interval, 1.25, 1.62) in men and 1.43 (1.25, 1.64) in women. This population-based study provides further evidence that fibrinogen and possibly factor VIII and von Willebrand factor are risk factors for cardiovascular disease.
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PMID:Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. 824 Nov 4


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