Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells
Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells
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DOI：
10.1093/eurheartj/ehq373
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发表时间：
2010-12-01
影响因子：
39.3
通讯作者：
Lerman, Amir
中科院分区：
文献类型：
--
作者：
Goessl, Mario;Moedder, Ulrike I.;Lerman, Amir
内皮祖细胞（EPC）可能参与受损冠状动脉内皮的修复。我们最近发现EPC共表达成骨细胞标志物骨钙素[OCN (+) EPC]，并发现其数量在早期和晚期冠状动脉粥样硬化患者中增加。目前的研究旨在检验早期冠状动脉粥样硬化与冠状循环内成骨 EPC 的滞留相关的假设。从 31 名接受侵入性冠状动脉内皮功能检测的患者的近端主动脉和冠状窦同时采集血样。使用流式细胞术分析外周血单核细胞的 EPC 标记物（CD133、CD34、KDR）和 OCN。 EPC 的净梯度通过将冠状动脉血流量乘以动静脉 EPC 梯度（负净梯度表明 EPC 保留）来计算。同样，分析血清样本中的基质细胞衍生因子 1 α (SDF-1 α) 和白细胞介素 8 (IL-8)，并计算它们的净产量。与对照组（n = 17）相比，内皮功能障碍患者（ED，n = 14）的 CD34+/CD133-/KDR+/OCN+ EPC 净保留量显着[118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00)，P = 0.004]。 OCN (+) EPC 的保留与 ED 程度相关。 ED 患者还表现出 CD34+/CD133-/KDR+ EPC 的净保留（P = 0.010）。 IL-8 的净产量在 ED 中呈阳性 [1540.80 (-300.40, 21744.10)pg/mL]，但在对照组中呈阴性 [-3428.50 (-11225.00, 647.48), P = 0.025]。我们的研究表明，早期冠状动脉粥样硬化患者的特点是 OCN (+) EPC 在冠状循环中滞留，可能导致进行性冠状动脉钙化而不是正常修复。
Endothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation.Blood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025].Our study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.