Impact of homocysteine-thiolactone on plasma fibrin networks.

Epidemiologic studies have shown that hyperhomocysteinemia is an independent risk factor for vascular disease. Homocysteine (Hcy) circulates as different species, mostly protein bound, and approximately 1% as its reduced form and the cyclic thioester homocysteine-thiolactone (HTL). Despite the level of plasma thiolactone being markedly low, detrimental effects are related to its high reactivity.

Alterations of fibrin network structure mediated by dermatan sulfate.

Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II (HCII) to enhance thrombin inhibition. It has also been reported that DS has a profibrinolytic effect. We have evaluated the effects of DS solutions (4-20 μg/mL) on the formation (by kinetic studies), structure (by electron microscopy and compaction assays) and lysis (with urokinase-type plasminogen activator) of plasma fibrin networks.

Homocysteine modifies fibrin clot deformability: another possible explanation of harm.

Several studies have associated elevated plasma homocysteine (Hcy) levels with higher risk of thrombosis. In order to evaluate possible changes in fibrin strength and deformability mediated by Hcy, the effect of the amino acid on plasma fibrin clot was studied, measuring the viscoelastic clots response as a function of Hcy concentration added to plasma (final concentrations: 0, 50, 100, 250 and 500 microM). Storage (G') and loss (G'') moduli were significantly higher than control at all Hcy concentrations evaluated in a dose-independent way (G'50 microM Hcy=254+/-10 Pa vs.

Impaired fibrin gel permeability by high homocysteine levels.

Mechanisms involved in the relationship between hyperhomocysteinemia and thrombosis are still unclear. In previous reports we have shown that high homocysteine concentrations led to more compact and branched fibrin networks than controls. These clots showed an impaired lysis associated to their architecture.

Plasma homocysteine cutoff values for venous thrombosis.

Background: Hyperhomocysteinemia is considered an independent risk factor for vascular occlusive diseases. To date, there is no general agreement on hyperhomocysteinemia cutoff values.

Methods: To establish a homocysteine cutoff value, we performed a case-control study in 118 patients suffering from venous thrombosis and in 115 healthy subjects.

Insight into the profibrinolytic activity of dermatan sulfate: effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators.

Introduction: Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II to enhance antithrombin action. It has also been suggested that DS has a profibrinolytic effect, although the exact molecular mechanism is as yet unknown.

Materials And Methods: An in vitro amidolytic method was used to study the effect of high and low molecular weight-DS on the activation of Glu and Lys-plasminogen by tissue and urinary plasminogen activators (t-PA and u-PA).

Influence of homocysteine on fibrin network lysis.

To elucidate some of the links between homocysteine and vascular disease, we have evaluated the effect of the amino acid on the formation (by kinetics studies), structure (by electron microscopy) and lysis of the fibrin network, using tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have studied whether homocysteine could alter the activity of the components involved in fibrinolysis (by amidolytic and thrombolytic methods). The results showed that homocysteine-associated networks were more compact and branched than controls (52 +/- 6 vs 44 +/- 5 fibers/field, P = 0.

Effects of homocysteine thiol group on fibrin networks: another possible mechanism of harm.

On the basis of growing clinical evidence, it is well known that elevated plasma homocysteine (Hcy) levels are associated with higher risk of venous and arterial thrombosis. Several experimental studies have been carried out in order to elucidate the mechanisms involved that still remain unclear. The aim of our study was to evaluate the homocysteine effects on formation and structure of plasmatic fibrin network.

The C677T thermolabile variant of methylene tetrahydrofolate reductase on homocysteine, folate and vitamin B12 in a hemodialysis center.

Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous.

Prevalence of hyperhomocysteinemia in an elderly population.

Background: Currently, total hyperhomocysteinemia (tHHcy) is a well-known condition linked to a higher risk of vascular disease. Prevalence of HHcy increases in elderly persons as the risk associated with it persists. Because factors can be potentially reduced in the elderly, it is important to carry out epidemiologic studies of HHcy.