Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Fisher rats were fed chow diets for two weeks after which they were divided into seven groups of ten rats each and fed 20% Canola, 20% menhaden, 20% partially hydrogenated soy oil (PHSO) or chow only, with or without 500 mg/Kg dietary vitamin E in chow containing 2% cholesterol for six weeks. Triglycerides were lower in the menhaden group and were essentially the same in the E supplemented groups as in their unsupplemented cohorts. Plasma cholesterol was higher in the Canola, and lower in the menhaden, groups, compared to the PHSO group. Cholesterol was the same in the E supplemented groups as in their unsupplemented cohorts. Plasma thiobarbituric acid reactant substances (TBARS) were higher in the menhaden group, compared to the chow group. Vitamin E supplementation lowered TBARS in the menhaden and PHSO groups, compared to the unsupplemented cohorts. Collagen induced platelet aggregation was lower in both Canola and menhaden groups, compared to the PHSO group. Vitamin E supplementation lowered collagen induced platelet aggregation only in the PHSO group. Thrombin induced platelet aggregation was lower in the Canola group, compared to the PHSO group. Vitamin E supplementation did not affect thrombin induced platelet aggregation compared to unsupplemented cohorts. Plasma vitamin E levels were lowest in the menhaden supplemented group compared to all other groups not receiving E, suggesting a greater requirement for E in this group. Finally, vitamin E supplementation raised the plasma E levels in all groups except the menhaden group when compared to unsupplemented cohorts.
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PMID:Effect of dietary menhaden, Canola and partially hydrogenated soy oil supplemented with vitamin E upon plasma lipids and platelet aggregation. 202 42

Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control subjects when 12-HETE synthesis was induced by thrombin or collagen, either in the presence or absence of indomethacin. Platelet conversion of exogenously added arachidonic acid (AA) to 12-HETE was not significantly different between the diabetic and control groups in the absence of indomethacin, although a small but significant increase in the conversion of AA to 12-HETE was present in the diabetic group platelets when indomethacin was added to the reaction. Vitamin E content was significantly reduced in platelets from the diabetic subjects, when compared with platelets from the control subjects, although plasma vitamin E levels were not significantly different between the two groups. Thrombin- and collagen-induced platelet 12-HETE synthesis demonstrated a significant negative linear correlation with platelet vitamin E content when measurements from both diabetic and control groups were combined. The above data suggest a relationship between low vitamin E content and increased 12-HETE synthesis in platelets from type I diabetic subjects.
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PMID:Production of 12-hydroxyeicosatetraenoic acid and vitamin E status in platelets from type I human diabetic subjects. 392 90

Diabetic subjects tend to develop microvascular complications believed to be due to platelet hyperaggregability. This increased platelet sensitivity is though to be the result of an imbalance of PGI2 and TXA2 production in diabetes. This study sought to determine whether megavitamin E supplementation could restore PGI2/TXA2 balance in streptozotocin-diabetic rats. Endogenous release of PGI2 by isolated aorta, determined via radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha, was significantly greater (P less than 0.05) in rats receiving 100x the normal vitamin E requirement than in untreated diabetic rats. PGI2 synthesis was negatively correlated with plasma glucose levels (r = -0.87, P less than 0.05) in non-fasted rats at sacrifice. Vitamin E supplementation, at both the 10x and the 100x level, significantly depressed (P less than 0.05) thrombin-stimulated synthesis of TXA2 in washed platelet. PGI2 and TXA2 production were expressed as a ratio. Megavitamin E therapy appears to increase this ratio over that seen in the diabetic animal. The data suggest that vitamin E, at high levels, exerts an ameliorating influence of the PGI2/TXA2 imbalance of diabetes.
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PMID:Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. 635 Jan 38

Although the effects of vitamin E on platelet function have been investigated in vivo and in vitro, vitamin E quinone, a natural metabolite of vitamin E, has been virtually overlooked. This oxidized form of vitamin E inhibits platelet aggregation and secretion induced by various aggregating agents more effectively than vitamin E by a magnitude of 5-10-fold. Vitamin E and vitamin E quinone do not alter platelet ultrastructure or cellular concentrations of serotonin and adenine nucleotides, including cAMP. Inhibition of aggregation by vitamin E quinone occurs in the absence of detectable reduction of vitamin E quinone or oxidation of vitamin E and is readily reversed by washing the platelet. Only vitamin E quinone prevents arachidonic acid release and slightly inhibits cyclooxygenase, whereas both agents partially prevent calcium release from a platelet subcellular organelle. Vitamin E quinone also inhibited synthesis of prostacyclin by endothelial cells with basal synthesis in the presence of external arachidonic acid being less affected than thrombin-stimulated PGI2 production. The greater potency of vitamin E quinone in suppressing platelet function compared to vitamin E suggests that this quinone metabolite may be the better antithrombotic agent and possibly responsible for in vivo effects previously attributed to vitamin E.
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PMID:The influence of vitamin E quinone on platelet structure, function, and biochemistry. 699 Oct 25

Although it has been reported that vitamin E (alpha-tocopherol) can reduce platelet adhesiveness and aggregation in vivo, the mechanism is still unknown. Therefore, the aim of the present study was to determine whether incubations of platelet-rich plasma (PRP) with vitamin E influence platelet adhesion to cultured endothelial cells. To exclude blood plasma involvement, also washed platelets were pretreated with alpha-tocopherol. Vitamin E (0.5-1.0 mM) was added to PRP or washed platelets. Endothelial cells in monolayer were incubated with thrombin-activated platelets (1 or 2 U/ml). After 1 hr of incubation, non-adhered platelets were removed and counted. Treating of PRP with alpha-tocopherol inhibited platelet adhesion to endothelial cell monolayer. This effect was dose dependent on concentrations of alpha-tocopherol and thrombin. In our experiments PRP was treated with alpha-tocopherol and endothelial cell monolayer was used as test surface. These findings agree with previous observations on the adhesivity of platelets to synthetic surfaces after dietary vitamin E in healthy volunteers. When washed platelets were incubated with alpha-tocopherol, no significant reduction of adhesion was detectable. As preincubation of washed platelets with alpha-tocopherol does not inhibit platelet adhesion, it may be supposed that the effect of vitamin E does not occur in a directly cellular mechanism. The data suggest that alpha-tocopherol may reduce platelet adhesiveness probably after incorporation by plasma lipoproteins.
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PMID:Vitamin E reduces platelet adhesion to human endothelial cells in vitro. 1093 56

Vitamin E is one of the most widely used antioxidants in cryopreservation and preservation technology. The objective of this study is to examine the effect of vitamin E on platelets and the coagulation system. Vitamin E was added at different concentrations in the range between 0.25 and 5 mM to donor plasma. Using a STA/STA Compact coagulation analyzer the following clotting tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). The control clotting times PT (13.80 +/- 0.4 s), APTT (27.4 +/- 2.4 s) and TT (17.6 +/- 0.4 s) remained unchanged in the presence of vitamin E. The effect of vitamin E on platelets was assessed by platelet-induced clot retraction (PICR) and aggregation by thrombin. PICR was unaffected by vitamin E. Platelet aggregation, however, was profoundly inhibited by vitamin E. We found that inhibition of platelet aggregation by vitamin E was concentration dependent: increasing with increasing vitamin E concentration. This inhibitory effect, however, was widely reversible upon dilution of vitamin E with autologous platelet-poor plasma.
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PMID:Effects of alpha-tocopherol on platelets and the coagulation system. 1167 55

The aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%. In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.
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PMID:Plasma protein oxidation is associated with an increase of procoagulant markers causing an imbalance between pro- and anticoagulant pathways in healthy subjects. 1184 57