Jin Cao, Lu Lin, Zhu Zheng Bin, Zhang Rui Yan, Zhang Qi, Du Run, Ding Feng Hua, Chen Qiu Jing, Shen Wei Feng
Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, PR China.
Coron Artery Dis. 2010 Aug;21(5):273-7. doi: 10.1097/MCA.0b013e32833b20f1.
This study sought to examine whether circulatory levels of endothelial dysfunction biomarkers [vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1)] are associated with occurrence of late or very late stent thrombosis (ST) after percutaneous coronary intervention with sirolimus-eluting stent implantation, and to assess the possible influence of genetic variants of these proteins on ST.
Serum levels of sVCAM-1, sICAM-1, sE-selectin, vWF, t-PA and PAI-1 were measured, and polymorphisms of vWF (-1234C/T, -1185A/G and -1051G/A), t-PA (insertion/deletion) and PAI-1 genes (4G/5G) were determined in 41 patients who experienced at least one episode of late or very late ST. Eighty-two patients without ST randomly selected from the same study period served as controls.
Serum levels of vWF, sVCAM-1 and sICAM-1 were significantly increased in patients with ST than in controls (all P<0.01). No significant difference was observed in the genotype and allele distribution of the vWF, t-PA and PAI-1 gene polymorphisms. Multivariable logistic regression analysis showed that vWF, sVCAM-1, discontinuation of clopidogrel therapy and left ventricular ejection fraction of less than 50% were independent determinants of late ST.
Increased serum vWF and sVCAM-1 levels are associated with late ST, suggesting that endothelial dysfunction contributes to the development of late or very late ST.
本研究旨在探讨内皮功能障碍生物标志物[血管细胞黏附分子(可溶性血管细胞黏附分子-1,sVCAM-1)、细胞间黏附分子(可溶性细胞间黏附分子-1,sICAM-1)、可溶性E-选择素、血管性血友病因子(vWF)、组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活剂抑制剂-1(PAI-1)]的循环水平是否与西罗莫司洗脱支架植入术后晚期或极晚期支架血栓形成(ST)的发生相关,并评估这些蛋白质的基因变异对ST的可能影响。
测定41例发生至少一次晚期或极晚期ST患者的血清sVCAM-1、sICAM-1、可溶性E-选择素、vWF、t-PA和PAI-1水平,并确定vWF基因(-1234C/T、-1185A/G和-1051G/A)、t-PA基因(插入/缺失)和PAI-1基因(4G/5G)的多态性。从同一研究期间随机选取82例无ST的患者作为对照。
ST患者的血清vWF、sVCAM-1和sICAM-1水平显著高于对照组(均P<0.01)。vWF、t-PA和PAI-1基因多态性的基因型和等位基因分布无显著差异。多变量逻辑回归分析显示,vWF、sVCAM-1、氯吡格雷治疗中断和左心室射血分数低于50%是晚期ST的独立决定因素。
血清vWF和sVCAM-1水平升高与晚期ST相关,提示内皮功能障碍促成了晚期或极晚期ST的发生。