Sakuma Masashi, Nasuno Takahisa, Abe Shichiro, Obi Syotaro, Toyoda Shigeru, Taguchi Isao, Sohma Ryoichi, Inoue Ken-Ichi, Nishino Setsu, Node Koichi, Attizzani Guiherme, Bezerra Hiram, Costa Marco, Simon Daniel, Inoue Teruo
Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
Research Support Center, Dokkyo Medical University, Mibu, Tochigi, Japan.
Int J Cardiol Heart Vasc. 2018 Feb 16;18:17-24. doi: 10.1016/j.ijcha.2017.12.003. eCollection 2018 Mar.
Bone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents.
In 63 patients undergoing coronary stent implantation, we measured circulating CD34 + CD133 + CD45low cells and serum levels of biomarkers relevant to stem cell mobilization. In 31 patients of them, we assessed vessel healing within the stented segment using optical coherence tomography (OCT) imaging. The CD34 + CD133 + CD45low cells increased 68 ± 59% 7 days after bare metal stent (BMS), 10 ± 53% after ZES ( < 0.01 vs BMS), 3 ± 49% after EES ( < 0.001 vs BMS), compared with baseline. Percent change in CD34 + CD133 + CD45low cells was positively correlated with that in stromal cell-derived factor (SDF)-1α ( = 0.29, = 0.034). Percentage of uncovered struts was higher in the EES group (14.4 ± 17.3%), compared with the BMS (0.7 ± 1.3, < 0.01) and ZES (0.4 ± 0.5, < 0.01) groups. The change in CD34 + CD133 + CD45low cells showed positive correlation with OCT-quantified mean neointimal area ( = 0.48, P < 0.01). Finally, circulating mononuclear cells obtained from 5 healthy volunteers were isolated to determine the effect of sirolimus, zotarolimus and everolimus on vascular cell differentiation. The differentiation of mononuclear cells into endothelial-like cells was dose-dependently suppressed by sirolimus, zotarolimus, and everolimus.
Mobilization of progenitor cells was suppressed, and differentiation of mononuclear cells into endothelial-like cells was inhibited, in association with increased number of uncovered stent struts, even after second generation drug-eluting stenting. These data suggest that new approaches are necessary to enhance stent healing.
骨髓来源的祖细胞可能有助于支架损伤血管部位的内皮细胞和平滑肌细胞依赖性愈合反应。本研究旨在评估佐他莫司洗脱支架（ZES）和依维莫司洗脱支架（EES）植入后祖细胞的动员和血管愈合情况。
在63例行冠状动脉支架植入术的患者中，我们检测了循环中的CD34 + CD133 + CD45low细胞以及与干细胞动员相关的生物标志物的血清水平。其中31例患者，我们使用光学相干断层扫描（OCT）成像评估支架段内的血管愈合情况。与基线相比，裸金属支架（BMS）植入后7天，CD34 + CD133 + CD45low细胞增加68±59%，ZES植入后增加10±53%（与BMS相比，P<0.01），EES植入后增加3±49%（与BMS相比，P<0.001）。CD34 + CD133 + CD45low细胞的百分比变化与基质细胞衍生因子（SDF）-1α的变化呈正相关（r = 0.29，P = 0.034）。与BMS组（0.7±1.3%）和ZES组（0.4±0.5%）相比，EES组未覆盖支架小梁的百分比更高（14.4±17.3%，P<0.01）。CD34 + CD133 + CD45low细胞的变化与OCT定量的平均新生内膜面积呈正相关（r = 0.48，P<0.01）。最后，从5名健康志愿者中分离出循环单核细胞，以确定西罗莫司、佐他莫司和依维莫司对血管细胞分化的影响。西罗莫司、佐他莫司和依维莫司均剂量依赖性地抑制单核细胞向内皮样细胞的分化。
即使在第二代药物洗脱支架植入后，祖细胞的动员受到抑制，单核细胞向内皮样细胞的分化受到抑制，同时未覆盖支架小梁的数量增加。这些数据表明需要新的方法来促进支架愈合。
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