Thrombostatin Inhibits Induced Canine Coronary Thrombosis
Thrombostatin Inhibits Induced Canine Coronary Thrombosis
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凝血酶抑制素可抑制犬冠状动脉血栓形成
DOI：
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发表时间：
1999
影响因子：
6.7
通讯作者：
A. Schmaier
中科院分区：
文献类型：
--
作者：
A. Hasan;S. Rebello;E. Smith;Sujata Srikanth;S. Werns;E. Driscoll;Jessica Faul;D. Brenner;D. Normolle;B. Lucchesi;A. Schmaier
Summary Thrombostatin (RPPGF), an angiotensin converting enzyme metabolite of bradykinin, is an inhibitor of α-thrombin’s ability to activate platelets. We examined the in vivo pharmacokinetics and pharmacodynamics of thrombostatin in rabbits and its ability to inhibit coronary thrombosis induced by electrolytic injury in dogs. Plasma half-life of thrombostatin had a t1/2α of 2.6 min and a t1/2β of 24 min in rabbits. Ligating the renal arteries did not prolong clearance (t1/2α = 2.4 min; t1/2β = 12 min). Thrombostatin produced a prolonged in vivo antiplatelet effect. At 30 min after a single intravenous administration in rabbits, thrombostatin’s plasma concentration was <8.7 μM (5 μg/ml). However, ex vivo 20 and 40 nM γ-thrombin-induced platelet aggregation of these rabbits’ platelets was inhibited 40% for 2.75 and 1 h, respectively. In vitro, flow cytometry studies revealed that thrombostatin specifically bound to human platelets and washed human platelets treated with thrombostatin were less responsive to γ-thrombin than control platelets. Using electrolytic injury to induce coronary artery thrombosis, dogs treated with thrombostatin, aspirin, or combined thrombostatin and aspirin occluded in 62 ± 25 (mean ± SD), 62 ± 36, or 89 ± 32 min versus untreated animals which occluded at 39 ± 27 min, (p <0.01, p <0.01 and p <0.001, respectively). These studies show that thrombostatin binds to platelets and can delay coronary occlusion in vivo. Abbreviations: RPPGF: thrombostatin; PAR1: protease activated receptor 1, the first cloned thrombin receptor; PRP: platelet-rich plasma; PPP: plateletpoor plasma; LCX: left circumflex coronary artery; APTT: activated partial thromboplastin time; PT: prothrombin time
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DOI：
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发表时间：
1997-10
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
S. Rebello;H. S. Blank;W. Rote;G. Vlasuk;B. Lucchesi
通讯作者：
S. Rebello;H. S. Blank;W. Rote;G. Vlasuk;B. Lucchesi
影响因子：
37.8
作者：
Hasan, AAK;Amenta, S;Schmaier, AH
通讯作者：
Schmaier, AH
激肽原的结构域 3 包含一个细胞结合位点和一个修饰血小板凝血酶活化的位点。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jiang,YP;Muller-Esterl,W;Schmaier,AH
通讯作者：
Schmaier,AH
高分子量激肽原通过抑制凝血酶与血小板的结合来抑制凝血酶诱导的血小板聚集和聚集蛋白的裂解。
影响因子：
20.3
作者：
Puri,RN;Zhou,F;Hu,CJ;Colman,RF;Colman,RW
通讯作者：
Colman,RW
低分子量激肽原与血小板结合，调节凝血酶诱导的血小板活化。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Meloni,FJ;Schmaier,AH
通讯作者：
Schmaier,AH