Riesinger Lisa, Saemisch Michael, Nickmann Markus, Methe Heiko
Department of Cardiology, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377, Munich, Germany.
Department of Internal Medicine, Kliniken Neumarkt, Neumarkt, Germany.
Heart Vessels. 2018 Dec;33(12):1559-1569. doi: 10.1007/s00380-018-1220-7. Epub 2018 Jul 12.
Bone marrow-derived endothelial progenitor cells (EPC) are released into the peripheral blood in situations of vascular repair/angiogenesis. Regulation of vascular repair and angiogenesis by EPC depends not only on the number of circulating EPC but also on their functionality. As endothelial cells can act as antigen-presenting cells in coronary artery disease (CAD), we postulated that EPC can be immune activated here as well. CD34-EPC were isolated from peripheral blood of patients with ST-elevation myocardial infarction (STEMI, n = 12), non-STEMI/unstable angina (UA, n = 15), and stable CAD (SA, n = 18). Expression of HLA-DR, adhesion and costimulatory molecules by isolated CD34-EPC were compared with levels in healthy controls (n = 18). There were no significant differences in VCAM-1 and CD80 expression by peripheral circulating CD34-EPC between the four groups, yet expression of CD86 was highest in UA (p < 0.05). ICAM-1 expression was lowest in SA (p < 0.01). CD34-EPC constitutively expressed HLA-DR across all groups. Of note, patients pretreated with HMG-CoA reductase inhibitors exhibited lower expression of VCAM-1 by CD34-EPC throughout all patient groups; furthermore, statins significantly limited ex vivo-induced upregulation of ICAM-1 by TNF-alpha. To the best of our knowledge, this is the first study to examine the expression of immune markers in peripheral circulating CD34-EPC ex vivo. We demonstrate that CD34-EPC display different patterns of adhesion and costimulatory molecules in various states of CAD. Expression levels were affected by pretreatment with statins. Hence, immune activity of peripheral circulating CD34 cells might play a pathophysiologic role in evolution of CAD.
骨髓来源的内皮祖细胞（EPC）在血管修复/血管生成的情况下会释放到外周血中。EPC对血管修复和血管生成的调节不仅取决于循环EPC的数量，还取决于它们的功能。由于内皮细胞在冠状动脉疾病（CAD）中可作为抗原呈递细胞，我们推测EPC在这里也可被免疫激活。从ST段抬高型心肌梗死（STEMI，n = 12）、非STEMI/不稳定型心绞痛（UA，n = 15）和稳定型CAD（SA，n = 18）患者的外周血中分离出CD34⁺-EPC。将分离出的CD34⁺-EPC上HLA-DR、黏附分子和共刺激分子的表达与健康对照者（n = 18）的水平进行比较。四组之间外周循环CD34⁺-EPC上VCAM-1和CD80的表达无显著差异，但UA组中CD86的表达最高（p < 0.05）。SA组中ICAM-1的表达最低（p < 0.01）。所有组中的CD34⁺-EPC均组成性表达HLA-DR。值得注意的是，在所有患者组中，接受HMG-CoA还原酶抑制剂预处理的患者，其CD34⁺-EPC上VCAM-1的表达较低；此外，他汀类药物显著限制了TNF-α在体外诱导的ICAM-1上调。据我们所知，这是第一项在体外检测外周循环CD34⁺-EPC中免疫标志物表达的研究。我们证明，CD34⁺-EPC在CAD的不同状态下表现出不同的黏附分子和共刺激分子模式。表达水平受他汀类药物预处理的影响。因此，外周循环CD34⁺细胞的免疫活性可能在CAD的发展中起病理生理作用。
