Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham, UK.
Thromb Haemost. 2010 Nov;104(5):1029-37. doi: 10.1160/TH09-11-0802. Epub 2010 Sep 13.
It was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patient's aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.
本研究旨在确定健康人群、稳定型冠心病患者、急性冠脉综合征患者及正常冠状动脉人群的血浆血红素氧合酶-1(HO-1)水平,并探讨其与血管生成素、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)和血管内皮生长因子的关系。采用酶联免疫吸附法(ELISA)检测 50 例健康对照者、30 例正常冠状动脉人群、70 例稳定型冠心病患者和 24 例急性冠脉综合征患者外周静脉枸橼酸盐血浆中的血浆标志物,并检测患者的主动脉根部、冠状动脉口、冠状窦和股动脉中的标志物。培养人脐静脉内皮细胞(HUVEC),并分别用肿瘤坏死因子(TNF)和血小板进行刺激。与健康对照组和正常冠状动脉人群相比,稳定型冠心病患者的 HO-1 水平升高(p<0.05),而急性冠脉综合征患者的 HO-1 水平进一步升高(p<0.01)。HO-1 仅与 MMP-9 相关,且仅在健康对照组中相关。在心脏或外周部位没有发现明显差异。HO-1 存在于 HUVEC 中及 24 小时 HUVEC 上清液中,但 TNF 可使其释放被抑制。血小板中不存在 HO-1。总之,HO-1 在稳定型冠心病和急性冠脉综合征中升高,可能来源于内皮细胞而非血小板。这可能对我们理解冠心病的病理生理学及其急性表现为急性冠脉综合征的机制具有重要意义。