Inhibition of coronary thrombosis and local inflammation by a noncarbohydrate selectin inhibitor.
Inhibition of coronary thrombosis and local inflammation by a noncarbohydrate selectin inhibitor.
复制标题
非碳水化合物选择素抑制剂抑制冠状动脉血栓形成和局部炎症。
DOI：
10.1152/ajpheart.2000.279.6.h3065
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Zoldhelyi,P;Beck,PJ;Bjercke,RJ;Ober,JC;Hu,X;McNatt,JM;Akhtar,S;Ahmed,M;ClubbJr,FJ;Chen,ZQ;Dixon,RA;Yeh,ET;Willerson,JT
我们验证了用阻断抗体或L、P和E选择素的小分子抑制剂甲氧基苯甲酰丙酸(MBPA)抑制选择素的假说，以防止犬冠脉病变模型中血栓的形成。采用犬冠状动脉左前降支挤压损伤和收缩所致的循环血流变异性(CFV)。全身注射P-选择素和L-选择素抗体后，分别有50%和17%的治疗犬CFV消失[P=无显著意义(NS)]。联合应用P-选择素和L-选择素抗体可抑制60%的治疗犬CFV(P=NS)。相反，静脉注射或局部外膜应用MBPA可显著降低CFV，并降低心肌髓过氧化物酶(MPO)活性。我们的结论是，小分子非碳水化合物抑制L-、P-和E-选择素的结合可显著减少动脉血栓形成，而全身应用L-和P-选择素抗体则不能复制这种抗血栓作用。这些结果强调了选择素在高切应力下动脉血栓形成中的作用，并提示抑制P-和L-选择素可能不足以防止该模型中的血栓形成。该模型中E-选择素在血栓形成中的作用有待进一步研究。
We tested the hypothesis that selectin inhibition with blocking antibodies or a small-molecular-weight inhibitor of L-, P-, and E-selectin, methoxybenzoylpropionic acid (MBPA), prevents thrombus formation in a canine coronary Folts' model. Cyclic flow variations (CFVs) were induced by crush injury and constriction of the left anterior descending coronary artery in dogs. Systemic infusion of antibodies to P- and L-selectin abolished CFVs, respectively, in 50% and 17% of treated dogs [P= not significant (NS)]. The combination of P- and L-selectin antibodies suppressed CFVs in 60% of treated dogs (P= NS). In contrast, systemic selectin blockade by intravenous infusion or local adventitial application of MBPA markedly reduced CFVs and, in addition, reduced myocardial myeloperoxidase (MPO) activity. We conclude that inhibition of L-, P-, and E-selectin binding by a small-molecular-weight, noncarbohydrate compound markedly reduces arterial thrombosis, whereas systemic administration of antibodies to L- and P-selectin fail to reproduce this antithrombotic effect. These results underscore the role of selectins in the pathogenesis of arterial thrombosis under high shear stress and suggest that inhibition of P- and L- selectin may not suffice to prevent thrombus formation in this model. The role of E-selectin in thrombus formation in this model awaits further testing.