Inoue Teruo, Sata Masataka, Hikichi Yutaka, Sohma Ryoichi, Fukuda Daiju, Uchida Toshihiko, Shimizu Minoru, Komoda Hiroshi, Node Koichi
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Circulation. 2007 Feb 6;115(5):553-61. doi: 10.1161/CIRCULATIONAHA.106.621714. Epub 2007 Jan 29.
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
We measured circulating CD34-positive mononuclear cells, activation of integrin Mac-1 on the surface of neutrophils, and plasma granulocyte-colony stimulating factor levels in 40 patients undergoing coronary stenting. After bare-metal stenting, CD34-positive cells increased, reaching a maximum on day 7 after stenting. The maximum change compared with baseline before stenting was more striking in patients with restenosis than without restenosis (332+/-108% versus 148+/-49%; P<0.05). In contrast, CD34-positive cells decreased after sirolimus-eluting stenting (72+/-21% on day 7). The change in CD34-positive cells on day 7 relative to baseline was closely correlated with that in activated Mac-1 at 48 hours (R=0.52, P<0.01) and that in granulocyte-colony stimulating factor levels at 24 hours (R=0.42, P<0.05). Cell culture assay on day 7 showed that mononuclear cells differentiated into CD31-positive endothelium-like cells after bare-metal stenting. In patients with restenosis, mononuclear cells differentiating into alpha-smooth muscle actin-positive smooth muscle-like cells also were observed. Implantation of sirolimus-eluting stents suppressed both types of differentiation.
Stent implantation may induce differentiation of bone marrow cells into endothelial or smooth muscle cells. Endothelial cells may participate in reendothelialization, a protective reaction against vascular injury, whereas smooth muscle cells may participate in neointimal thickening and restenosis. Sirolimus-eluting stents appear to inhibit the mobilization and differentiation of bone marrow cells.
最近，越来越多的证据表明骨髓来源的干细胞能够分化为血管细胞。据推测，血管损伤后的炎症反应会触发骨髓中内皮祖细胞和平滑肌祖细胞的动员。
我们检测了40例接受冠状动脉支架置入术患者的循环CD34阳性单核细胞、中性粒细胞表面整合素Mac-1的活化情况以及血浆粒细胞集落刺激因子水平。裸金属支架置入术后，CD34阳性细胞增加，在支架置入后第7天达到最大值。与无再狭窄患者相比，再狭窄患者支架置入后与基线相比的最大变化更为显著（332±108%对148±49%；P<0.05）。相比之下，西罗莫司洗脱支架置入术后CD34阳性细胞减少（第7天为72±21%）。第7天CD34阳性细胞相对于基线的变化与48小时时活化的Mac-1变化密切相关（R=0.52，P<0.01），与24小时时粒细胞集落刺激因子水平变化密切相关（R=0.42，P<0.05）。第7天的细胞培养试验表明，裸金属支架置入术后单核细胞分化为CD31阳性的内皮样细胞。在再狭窄患者中，还观察到单核细胞分化为α-平滑肌肌动蛋白阳性的平滑肌样细胞。西罗莫司洗脱支架的植入抑制了这两种类型的分化。
支架植入可能诱导骨髓细胞分化为内皮细胞或平滑肌细胞。内皮细胞可能参与再内皮化，这是一种针对血管损伤的保护反应，而平滑肌细胞可能参与内膜增厚和再狭窄。西罗莫司洗脱支架似乎抑制骨髓细胞的动员和分化。
