Radecke Christopher E, Warrick Alexandra E, Singh Gagan D, Rogers Jason H, Simon Scott I, Armstrong Ehrin J
Scott I. Simon, Department of Biomedical Engineering, University of California at Davis, 451 East Health Sciences Drive, Davis, CA 95616, USA, Tel.: +1 530 752 0299, E-mail
Thromb Haemost. 2015 Mar;113(3):605-16. doi: 10.1160/TH14-02-0151. Epub 2014 Nov 20.
Coronary artery disease (CAD) is characterised by progressive atherosclerotic plaque leading to flow-limiting stenosis, while myocardial infarction (MI) occurs due to plaque rupture or erosion with abrupt coronary artery occlusion. Multiple inflammatory pathways influence plaque stability, but direct assessment of endothelial inflammation at the site of coronary artery stenosis has largely been limited to pathology samples or animal models of atherosclerosis. We describe a technique for isolating and characterising endothelial cells (ECs) and EC microparticles (EMPs) derived directly from the site of coronary artery plaque during balloon angioplasty and percutaneous coronary intervention. Coronary artery endothelial cells (CAECs) were identified using imaging flow cytometry (IFC), and individual CAEC and EMP expression of the pro-atherogenic adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) was assessed immediately following angioplasty. Patients with MI registered 73 % higher VCAM-1 expression on their CAECs and 79 % higher expression on EMPs compared to patients with stable CAD. In contrast, VCAM-1 expression was absent on ECs in the peripheral circulation from these same subjects. VCAM-1 density was significantly higher on CAECs and EMPs among patients with MI and positively correlated with markers of myocardial infarct size. We conclude that increased VCAM-1 expression on EC and formation of EMP at the site of coronary plaque is positively correlated with the extent of vascular inflammation in patients with myocardial infarction.
冠状动脉疾病(CAD)的特征是动脉粥样硬化斑块逐渐进展,导致血流受限性狭窄,而心肌梗死(MI)则是由于斑块破裂或糜烂伴冠状动脉突然闭塞所致。多种炎症途径影响斑块稳定性,但对冠状动脉狭窄部位内皮炎症的直接评估在很大程度上仅限于病理样本或动脉粥样硬化动物模型。我们描述了一种在球囊血管成形术和经皮冠状动脉介入治疗期间直接从冠状动脉斑块部位分离和表征内皮细胞(ECs)和EC微粒(EMPs)的技术。使用成像流式细胞术(IFC)鉴定冠状动脉内皮细胞(CAECs),并在血管成形术后立即评估单个CAEC和促动脉粥样硬化黏附分子血管细胞黏附分子-1(VCAM-1)的EMP表达。与稳定型CAD患者相比,MI患者的CAEC上VCAM-1表达高73%,EMPs上表达高79%。相比之下,这些相同受试者外周循环中的ECs上不存在VCAM-1表达。MI患者的CAECs和EMPs上的VCAM-1密度显著更高,且与心肌梗死面积标志物呈正相关。我们得出结论,冠状动脉斑块部位EC上VCAM-1表达增加和EMP形成与心肌梗死患者的血管炎症程度呈正相关。