Division of Nephrology, Hypertension & Transplantation, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2013 Dec 2;8(12):e81595. doi: 10.1371/journal.pone.0081595. eCollection 2013.
In women with ischemia and no obstructive coronary artery disease, the Women's Ischemic Syndrome Evaluation (WISE) observed that microvascular coronary dysfunction (MCD) is the best independent predictor of adverse cardiovascular events. Since coronary microvascular tone is regulated in part by endothelium, we hypothesized that circulating endothelial cells (CEC), which reflect endothelial injury, and the number and function of bone-marrow derived angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve as biomarkers for decreased coronary flow reserve (CFR) and MCD.
We studied 32 women from the WISE cohort. CFR measurements in response to intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC colonies and CEC in peripheral blood samples. BMDAC function was assessed by assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable nitric oxide (NO). These findings were compared with a healthy reference group and also entered into a multivariable model with CFR as the dependent variable.
Compared with a healthy reference group, women with MCD had lower numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936 (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis showed strong correlation of CFR to the combination of BMDAC colony count and CD34+ cell function (migration and NO) (R(2) = 0.45; P<0.05).
The BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women with MCD and are independently associated with CFR. These circulating cells may provide mechanistic insights into MCD in women with ischemia.
在无阻塞性冠状动脉疾病但存在缺血的女性中，女性缺血综合征评估（WISE）观察到微血管冠状动脉功能障碍（MCD）是不良心血管事件的最佳独立预测因子。由于冠状动脉微血管张力部分受内皮调节，我们假设反映内皮损伤的循环内皮细胞（CEC）和有助于修复受损内皮的骨髓来源的血管生成细胞（BMDAC）的数量和功能可能作为冠状动脉血流储备（CFR）和 MCD 降低的生物标志物。
我们研究了来自 WISE 队列的 32 名女性。通过测量冠状动脉内腺苷反应的 CFR 来评估 MCD。我们计数外周血样本中的 BMDAC 集落和 CEC。通过 CD34+细胞向 SDF-1 的迁移测定和生物可利用性一氧化氮（NO）的测量来评估 BMDAC 功能。将这些发现与健康参考组进行比较，并将其纳入 CFR 作为因变量的多变量模型中。
与健康参考组相比，MCD 女性的 BMDAC 集落数量较少[16（0，81）比 24（14，88）；P=0.01]，NO 也较少[936（156，1875）比 1168（668，1823）；P=0.02]。多变量回归分析显示，CFR 与 BMDAC 集落计数和 CD34+细胞功能（迁移和 NO）的组合密切相关（R2=0.45；P<0.05）。
有 MCD 症状的女性中 BMDAC 功能和 BMDAC 集落数量减少，并且与 CFR 独立相关。这些循环细胞可能为女性缺血性 MCD 的发病机制提供深入了解。
