Characterization of the Anticoagulant and Antithrombotic Properties of the Sphingosine 1-Phosphate Mimetic FTY720.
Sphingosine 1-phosphate (S1P) is a highly active lysophospholipid implicated in various cardiocerebrovascular events such as coagulation, myocardial infarction and stroke. However, as the functional S1P receptor antagonist, whether the S1P mimetic FTY720 can modulate coagulation and/or thrombotic formation remains largely unknown. We investigated the effects of FTY720 on adenosine diphosphate (ADP)-induced platelet aggregation, coagulation parameters and thrombus formation in rats. Pretreatment with FTY720 (2.5 mg/kg) inhibited platelet aggregation induced by ADP, elongated the thrombin time and decreased the fibrinogen levels. However, FTY720 produced no significant effects on the arteriovenous bypass thrombus formation or the FeCl3-induced thrombus formation in the inferior vena cava and the common carotid artery. Our data suggest that FTY720 can exert an inhibitory effect on platelet aggregation and coagulation-related parameters. These characteristics of FTY720 could be useful as an adjunct in the treatment of ischemic diseases such as ischemic stroke and myocardial infarction.
The State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
Zhen
Z
Zhao
Ruixue
R
Wang
Zhijun
Z
Huo
Chunlei
C
Li
Zhiyong
Z
Wang
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001166:Arteriovenous Shunt, Surgical; D040761:Biomimetic Materials; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000244:Adenosine Diphosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; C024555:ferric chloride