Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Neurosci Res. 2012 Sep;90(9):1788-93. doi: 10.1002/jnr.23068. Epub 2012 Apr 19.
Endothelial progenitor cells (EPC) have been associated with good functional outcome in ischemic stroke. From preclinical studies, it has been reported that EPC proliferation is mediated by several molecular markers, including vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), and the activity of matrix metalloproteinase-9 (MMP-9). Therefore, our aim was to study the role of these molecular factors in EPC proliferation in human ischemic stroke. Forty-eight patients with first episode of nonlacunar ischemic stroke were prospectively included in the study within 12 hr of symptom onset. EPC colonies were classified as early-outgrowth colony forming unit-endothelial cell (CFU-EC) and quantified at admission, at 24 and 72 hr, at day 7, and at 3 months. At the same time, serum levels of VEGF, SDF-1α, and active MMP-9 were measured by ELISA. The primary endpoint was EPC increment during the first week, which was defined as the difference in the number of CFU-EC between day 7 and admission. We found that VEGF (r = 0.782), SDF-1α (r = 0.828), and active MMP-9 (r = 0.740) levels at 24 hr from stroke onset showed a strong correlation with EPC increment. Similar results were found for VEGF levels at 72 hr (r = 0.839) and at day 7 (r = 0.602) as well as for active MMP-9 levels at 72 hr (r = 0.442) and at day 7 (r = 0.474). In the multivariate analyses, serum levels of VEGF at 72 hr (B: 0.074, P < 0.0001) and SDF-1α at 24 hr (B: 0.049, P = 0.008) were independent factors for EPC increment during the first week of evolution. These findings suggest that VEGF and SDF-1α may mediate EPC proliferation in human ischemic stroke.
内皮祖细胞（EPC）与缺血性脑卒中的良好功能结局相关。从临床前研究来看，已经有报道称 EPC 的增殖是由多种分子标志物介导的，包括血管内皮生长因子（VEGF）、基质细胞衍生因子-1α（SDF-1α）和基质金属蛋白酶-9（MMP-9）的活性。因此，我们的目的是研究这些分子因素在人类缺血性脑卒中 EPC 增殖中的作用。48 例首发非腔隙性缺血性脑卒中患者在症状发作后 12 小时内前瞻性纳入研究。EPC 集落被分类为早期外生集落形成单位-内皮细胞（CFU-EC），并在入院时、24 小时、72 小时、第 7 天和第 3 个月进行定量。同时，通过 ELISA 测量血清 VEGF、SDF-1α 和活性 MMP-9 的水平。主要终点是第一周内 EPC 的增加量，定义为第 7 天与入院时 CFU-EC 数量的差异。我们发现，卒中发病后 24 小时的 VEGF（r = 0.782）、SDF-1α（r = 0.828）和活性 MMP-9（r = 0.740）水平与 EPC 增加量呈强相关。VEGF 水平在 72 小时（r = 0.839）和第 7 天（r = 0.602）以及活性 MMP-9 水平在 72 小时（r = 0.442）和第 7 天（r = 0.474）也得到了类似的结果。在多变量分析中，血清 VEGF 水平在 72 小时（B：0.074，P < 0.0001）和 SDF-1α 水平在 24 小时（B：0.049，P = 0.008）是 EPC 在发病后第一周内增加的独立因素。这些发现表明，VEGF 和 SDF-1α 可能介导人类缺血性脑卒中的 EPC 增殖。
