prevents pulmonary thrombosis prevents is egcg active on thrombin (th) ? without changing...

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prevents prevents pulmonary thrombosis pulmonary thrombosis Is EGCG active on thrombin (Th) ? Is EGCG active on thrombin (Th) ? without changing without changing coagulation parameters coagulation parameters (proTh and Th-time) (proTh and Th-time) inhibits inhibits platelet platelet aggregation aggregation Kang Kang et al et al ., Throm.Res. 96, 229-237, 1999 ., Throm.Res. 96, 229-237, 1999 2.2 mM 2.2 mM ( thrombin > fibrinogen > fibrin > clot ) ( thrombin > fibrinogen > fibrin > clot ) Garbisa 2001

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Page 1: prevents pulmonary thrombosis prevents Is EGCG active on thrombin (Th) ? without changing coagulation parameters (proTh and Th-time) without changing

prevents prevents pulmonary thrombosispulmonary thrombosis

prevents prevents pulmonary thrombosispulmonary thrombosis

Is EGCG active on thrombin (Th) ?Is EGCG active on thrombin (Th) ?Is EGCG active on thrombin (Th) ?Is EGCG active on thrombin (Th) ?

without changing without changing coagulation parameterscoagulation parameters

(proTh and Th-time)(proTh and Th-time)

without changing without changing coagulation parameterscoagulation parameters

(proTh and Th-time)(proTh and Th-time)

inhibits inhibits platelet platelet

aggregationaggregation

inhibits inhibits platelet platelet

aggregationaggregation

Kang Kang et alet al., Throm.Res. 96, 229-237, 1999., Throm.Res. 96, 229-237, 1999

2.2 mM2.2 mM

( thrombin > fibrinogen > fibrin > clot )( thrombin > fibrinogen > fibrin > clot )

Garbisa 2001

Page 2: prevents pulmonary thrombosis prevents Is EGCG active on thrombin (Th) ? without changing coagulation parameters (proTh and Th-time) without changing

0

25

50

75

100%

en

zym

atic

act

ivit

y

0.1 1 10 100 1000 10000

EGCG [M]

LETh cath.G MMP-

2 uPA (Jankun ‘97)

Differential enzyme inhibition by EGCGDifferential enzyme inhibition by EGCGDifferential enzyme inhibition by EGCGDifferential enzyme inhibition by EGCG

EGCG useful in clinical application (inflammation),EGCG useful in clinical application (inflammation),preserving cathepsin G- or uPA-mediated reactionspreserving cathepsin G- or uPA-mediated reactions

(Kang ‘99)

Is EGCG directly active on thrombin (Th) ?Is EGCG directly active on thrombin (Th) ?Is EGCG directly active on thrombin (Th) ?Is EGCG directly active on thrombin (Th) ?

MMP-12 (Demeule ‘00)

??

otherother serine-proteinases serine-proteinases metallo-proteinasesmetallo-proteinases

(Sartor L., Pezzato E., Garbisa S., submitted to J.Leuk.Biol. 2001)

Garbisa 2001