González-Fernández F, López-Farré A, Rodríguez-Feo J A, Farré J, Guerra J, Fortes J, Millás I, García-Durán M, Rico L, Mata P, de Miguel L S, Casado S
Nephrology, Hypertension and Cardiovascular Research Laboratory, the Department of Cardiology, and the Department of Pathology Madrid, Spain.
Circ Res. 1998 Nov 30;83(11):1080-7. doi: 10.1161/01.res.83.11.1080.
There is functional evidence suggesting that endothelial denudation stimulates inducible nitric oxide synthase (iNOS) activity in the vascular wall. In vitro studies have shown that iNOS expression in smooth muscle cells is reduced by endothelial cells. In the present study we have analyzed the time course of iNOS protein expression in the arterial wall after in vivo deendothelialization. Endothelial denudation was performed in the left carotid artery of Wistar rats, and the right carotid artery was used as control. Whereas iNOS protein was weakly expressed 6, 24, and 48 hours after endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after vascular damage. Because platelet adhesion and aggregation occur early after endothelial damage, we studied the role of activated platelets in the negative modulation of iNOS protein expression during the first 2 days after endothelial denudation. Early after in vivo endothelial injury, platelet-depleted rats showed a marked iNOS protein expression in the vascular wall. Similar results were obtained by blocking the platelet glycoprotein (GP) IIb/IIIa. Although iNOS protein is present in the arterial wall several days after endothelial denudation, early after arterial wall injury iNOS protein is weakly expressed. Platelets play a crucial role in preventing iNOS protein expression early after endothelial damage, an effect that can be avoided with GP IIb/IIIa blockers. Although iNOS protein was weakly expressed in vivo in the rat carotid artery wall 6, 24, and 48 hours after balloon endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after arterial damage. iNOS expression could be increased early after endothelial injury by removing circulating platelets and by an antibody against the GP IIb/IIIa. In conclusion, platelets prevent iNOS protein expression early after endothelial balloon damage, an effect that can be avoided with GP IIb/IIIa blocking agents.
有功能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。体外研究表明，内皮细胞可降低平滑肌细胞中iNOS的表达。在本研究中，我们分析了体内内皮剥脱后动脉壁中iNOS蛋白表达的时间进程。在Wistar大鼠的左颈动脉进行内皮剥脱，右颈动脉用作对照。内皮剥脱后6、24和48小时，iNOS蛋白表达较弱，而在血管损伤后7、14和30天，发现iNOS表达明显。由于内皮损伤后早期会发生血小板黏附和聚集，我们研究了活化血小板在内皮剥脱后前两天对iNOS蛋白表达的负调节作用。体内内皮损伤后早期，血小板耗竭的大鼠在血管壁中显示出明显的iNOS蛋白表达。通过阻断血小板糖蛋白（GP）IIb/IIIa也获得了类似的结果。尽管内皮剥脱后数天iNOS蛋白存在于动脉壁中，但动脉壁损伤后早期iNOS蛋白表达较弱。血小板在内皮损伤后早期防止iNOS蛋白表达中起关键作用，使用GP IIb/IIIa阻滞剂可避免这种作用。尽管在球囊内皮剥脱后6、24和48小时，大鼠颈动脉壁中iNOS蛋白在体内表达较弱，但在动脉损伤后7、14和30天，发现iNOS表达明显。通过去除循环血小板和使用抗GP IIb/IIIa抗体，可在内皮损伤后早期增加iNOS表达。总之，血小板在内皮球囊损伤后早期防止iNOS蛋白表达，使用GP IIb/IIIa阻断剂可避免这种作用。
