Selective determination of α2-plasmin inhibitor activity in plasma using chromogenic substrate

Matsuda, Tamotsu; Ogawara, Midori; Miura, Reiko; Seki, Toshiko; Matsumoto, Takashi; Teramura, Yasuo; Nakamura, Kazumitsu

doi:10.1016/0049-3848(84)90077-x

Cited by 31 publications

(9 citation statements)

References 11 publications

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“…␣-2-Antiplasmin. The standard chromogenic method for measuring ␣-2-antiplasmin requires a blood sample by using a citrate-based anticoagulant (16). No ELISA-based method for ␣-2-antiplasmin determination is available.…”

Section: Resultsmentioning

confidence: 99%

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Moore¹,

Krokhin

Beavis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Fabry disease is inherited as an X-linked disorder secondary to deficiency of ␣-galactosidase A, resulting in abnormal metabolism of substances containing ␣-D-galactosyl moieties. As a consequence, a multisystem disorder develops, culminating in strokes, progressive renal, and cardiac dysfunction. Signs and symptoms of Fabry disease become manifest in childhood, but diagnosis is often delayed. Thirteen children with Fabry disease (age range, 6.5-17 years) were studied as part of a 6-month open-label study of enzyme replacement therapy (ERT) with agalsidase alfa. Paired serum samples were drawn at the start of the study and after 6 months of ERT. Global protein changes in paired samples were compared by using differential stable isotope labeling of peptide lysine residues with O-methylisourea and subsequent nanoHPLCtandem MS. Statistically significant decreases were observed for five proteins following ERT: ␣2-HS glycoprotein, vitamin D-binding protein, transferrin, Ig-␣-2 C chain, and ␣-2-antiplasmin. The presence of low levels of ␣-2-antiplasmin and plasminogen was confirmed by alternate means in 34 consecutive patients, including four of five ERT-naïve subjects. Decreased ␣-2-antiplasmin was associated with a parallel increase in circulating VEGF. Soluble VEGF receptor-2 was significantly elevated in plasma of patients compared with pediatric controls and decreased with ERT. These results suggest previously unknown abnormalities of fibrinolysis and angiogenesis factors in Fabry disease. We demonstrated the feasibility of identifying treatment-specific alterations in a small number of subjects that point to previously unsuspected diseaserelated biological abnormalities.disease-specific alteration ͉ enzyme replacement ͉ vasculopathy

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Section: Resultsmentioning

confidence: 99%

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Moore¹,

Krokhin

Beavis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…The D-dimer concentration, which was determined to be less than the detection limit (0.5 g/ml), was assumed to be 0.5 g/ml for the purpose of statistical analysis. Plasma ␣2-antiplasmin activity was determined using the Enzyme test of APL2 kit (Matsuda et al, 1984) (Daiichi Chemical, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Enhancement of Fibrinolysis by EF6265 [(S)-7-Amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl] methyl]heptanoic Acid], a Specific Inhibitor of Plasma Carboxypeptidase B

Suzuki¹,

Muto²,

Fushihara³

et al. 2004

J Pharmacol Exp Ther

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Plasma procarboxypeptidase B, also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is converted by thrombin into the active enzyme, carboxypeptidase B (CPB)/activated TAFI. Plasma CPB down-regulates fibrinolysis by removing carboxy-terminal lysines, the ligands for plasminogen and tissue-type plasminogen activator (tPA), from partially degraded fibrin. To target thrombosis in a new way, we have identified and optimized a phosphinic acid-containing inhibitor of CPB,heptanoic acid] and determined both the pharmacological profile and pathophysiological role of CPB in rat thrombolysis. EF6265 specifically inhibited plasma CPB activity with an IC 50 (50% inhibitory concentration) of 8.3 nM and enhanced tPA-mediated clot lysis in a concentrationdependent manner. EF6265 decreased detectable thrombi (percentage of glomerular fibrin deposition; control, 98 Ϯ 1.1; EF6265, 0.1 mg/kg, 27 Ϯ 9.1) that had been generated by tissue factor in a rat microthrombosis model with concomitant increases in plasma D-dimer concentration (control, Ͻ0.5 g/ml; EF6265, 0.1 mg/kg, 15 Ϯ 3.5 g/ml). EF6265 reduced plasma ␣2-antiplasmin activity to a lesser extent than tPA. In an arteriovenous shunt model, EF6265 (1 mg/kg) enhanced exogenous tPA-mediated thrombolysis under the same conditions that neither EF6265 nor tPA (600 kIU/kg) alone reduced thrombi. EF6265 (1 and 30 mg/kg) did not affect the bleeding time in rats. Moreover, it did not prolong the bleeding time evoked by tPA (600 kIU/kg). These results confirm that circulating procarboxypeptidase B functions as a fibrinolysis inhibitor's zymogen and validates the use of CPB inhibitors as both an enhancer of physiological fibrinolysis in microcirculation and as a novel adjunctive agent to tPA for thromboembolic diseases while maintaining a small effect on primary hemostasis.Thrombosis-related diseases, including myocardial infarction, cerebral infarction, and disseminated intravascular coagulation are life-threatening and the search for treatments remains challenging. Although thrombolytics including tissue-type plasminogen activator (tPA) or urokinase-type plasminogen activator and anticoagulants including heparin have been developed over the last few decades, the risk of hemorrhaging with these antithrombotic agents restricts their clinical use. The dose of tPA must be high enough to overcome the inhibitory effects of plasminogen activator inhibitor-1 in the plasma, and results in the generation of plasmin in circulating blood (Rijken and Sakharov, 2001). Consequently, these large quantities of generated plasmin can induce thrombolysis and result in hemorrhaging as a side effect (Bloom et al., 1988). Many efforts have therefore been made to identify and develop pharmacologically distinct antithrombotic agents while maintaining a low risk of hemorrhaging.Plasma procarboxypeptidase B (proCPB; EC 3.4.17.20), also known as thrombin-activatable fibrinolysis inhibitor (TAFI) or procarboxypeptidase U, is produced in the liver and Article, publication date, and citation informa...

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“…13 - 16 Plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer were determined using commercially available enzyme-linked immunosorbent assay kits (Behringwerke A.G., Marburg, F.R.G. 17 and MAbCO, Springwood, Australia respectively).…”

Section: Methodsmentioning

confidence: 99%

Activation of coagulation in acute cardioembolic stroke.

Takano

Yamaguchi

Kato

et al. 1991

Stroke

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The hematologic disorders in patients with acute cardioembolic stroke are not fully understood, and no reliable measures are available to identify patients at high risk for recurrent embolism. We analyzed coagulation and fibrinolytic functions in 22 patients with cardiogenic cerebral embolism ^24 hours after onset and in 25 age-matched controls. The levels of antithrombin HI, protein C, and a^-plasmin inhibitor were significantly lower in the patients than in the controls (/?<0.001, 0.02, and 0.05, respectively). In contrast, the plasma concentrations of thrombinantithrombin i n complex and crosslinked D-dimer were markedly higher in the patients than in the controls (p<0.01 and 0.001, respectively). At the time of admission, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer in the eight patients at high risk for recurrent embolization (one with prodromal embolism, three with intracardiac thrombi, and four with recurrent embolization) were 2.8 and 3.5 times, respectively, higher than those in the 14 patients without recurrence or thrombus formation. The lowest concentration of crosslinked D-dimer in the eight patients at high risk for recurrent embolization was 600 ng/ml on admission. Our results suggest that patients with acute cardioembolic stroke have various degrees of consumption coagulopathy and that the plasma concentrations of thrombin-antithrombin HI complex and crosslinked D-dimer can be useful indicators of those who are prone to recurrent embolization during this stage. (Stroke 1991^2:12-16)

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Selective determination of α2-plasmin inhibitor activity in plasma using chromogenic substrate

Cited by 31 publications

References 11 publications

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Enhancement of Fibrinolysis by EF6265 [(S)-7-Amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl] methyl]heptanoic Acid], a Specific Inhibitor of Plasma Carboxypeptidase B

Activation of coagulation in acute cardioembolic stroke.

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