González-Fernández F, Rodríguez-Feo J A, Farré J, Guerra J, Romero J, Gómez J, Rico L, Ayala R, Marcos P, Sánchez de Miguel L, Casado S, López-Farré A
Laboratorio de Nefrología, Hipertensión e Investigación Cardiovascular, Fundación Jiménez Díaz, Madrid.
Rev Esp Cardiol. 1999 Jun;52(6):422-8. doi: 10.1016/s0300-8932(99)74940-7.
Functional evidence suggests that endothelial denudation stimulates inducible nitric oxide synthase (iNOS) activity in the vascular wall. In vitro studies done in our laboratory have shown that iNOS expression in smooth muscle cells is reduced by endothelial cells. The object of this study was to analyze the iNOS protein expression in the arterial wall after in vivo deendothelialization, and the role of platelet activation abciximab in the expression of this protein.
Endothelial denudation was performed in the left carotid artery of Wistar rats. The right carotid artery was used as control.
iNOS protein was only weakly expressed at 6, 24 and 48 hours after endothelial denudation. Since platelet adhesion and aggregation occur early after endothelial damage, we have analyzed the role of activated platelets in iNOS protein expression during the first two days after angioplasty. Early after in vivo endothelial injury, thrombocytopenic rats showed a marked iNOS protein expression. Similar results were obtained by blocking the platelet glycoprotein IIb/IIIa in rats treated with abciximab (Reopro).
iNOS protein is weakly expressed in the arterial wall after endothelial denudation. Platelets play a crucial role preventing iNOS protein expression early after endothelial damage through a mechanism that depends on GP IIb/IIIa, an effect that can be avoided with glycoprotein IIb/IIIa, blockers, such as abciximab.
功能学证据表明,内皮剥脱可刺激血管壁中诱导型一氧化氮合酶(iNOS)的活性。我们实验室进行的体外研究表明,内皮细胞可降低平滑肌细胞中iNOS的表达。本研究的目的是分析体内内皮剥脱后动脉壁中iNOS蛋白的表达情况,以及血小板激活剂阿昔单抗在该蛋白表达中的作用。
对Wistar大鼠的左颈动脉进行内皮剥脱。以右颈动脉作为对照。
内皮剥脱后6小时、24小时和48小时,iNOS蛋白仅微弱表达。由于血小板黏附和聚集在内皮损伤后早期就会发生,我们分析了血管成形术后前两天活化血小板在iNOS蛋白表达中的作用。体内内皮损伤后早期,血小板减少的大鼠显示出明显的iNOS蛋白表达。在用阿昔单抗(Reopro)治疗的大鼠中,通过阻断血小板糖蛋白IIb/IIIa也获得了类似结果。
内皮剥脱后,iNOS蛋白在动脉壁中微弱表达。血小板在内皮损伤后早期通过一种依赖于糖蛋白IIb/IIIa的机制在阻止iNOS蛋白表达方面起关键作用,而使用糖蛋白IIb/IIIa阻滞剂(如阿昔单抗)可避免这种作用。