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Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation.

Abstract：

:Algal fucoidans possess a wide variety of biological activities, including anticoagulation and antithrombosis, making them potential candidates for clinical use. We assessed the antiaggregant, anticoagulant and antithrombotic activities and the underlying mechanism of the low- and high-molecular weight fucoidans from the seaweed Laminaria japonica of Qingdao, China (F-Q and HMWF-Q). In the platelets of rats and humans, HMWF-Q demonstrated a pro-aggregation response, whereas F-Q (like the commercially purchased fucoidan (F-S) and heparin), showed an inhibitory effect on thrombin-induced aggregation with an IC(50) of 8 microg/mL, approximately five times lower than those of F-S and heparin. In the activated partial thromboplastin time test, F-Q (40 microg/mL) demonstrated less potent effect than F-S (40 microg/mL) and heparin (7mug/mL); 162+/-2.4s vs. 250+/-13.2s and >300s, p<0.01, respectively. It was also less effective than F-S on inhibiting thrombin catalyzed fibrinogen cleavage (IC(50) 10 microg/mL vs. 2.8 microg/mL) in vitro and rat thrombosis in vivo at 3mg/kg (i.v.). The inhibitory effects of F-Q and heparin on thrombin activity were strikingly enhanced by either antithrombin (AT) or heparin cofactor II (HCII). A direct interaction of F-S with thrombin, and F-Q or heparin with AT was demonstrated in both fluorescence quenching and PAGE analysis. Additionally, a pro-aggregation effect and an enhancement of thrombin activity were also observed with F-S, but not with F-Q or heparin, treatment. These results indicate that F-Q inhibits thrombin via activation of AT and HCII, whereas F-S mainly interacts directly with thrombin. Importantly, F-Q shows a higher specificity for hypoaggregation and a weaker effect for anticoagulant profiles than heparin and F-S. Therefore, F-Q could be a promising candidate for the treatment of thrombosis-related cardiovascular diseases.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Zhu Z,Zhang Q,Chen L,Ren S,Xu P,Tang Y,Luo D

doi

10.1016/j.thromres.2010.02.011

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

419-26

issue

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(10)00158-1

journal_volume

125

pub_type

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Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation.