Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.
Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.
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DOI：
10.1371/journal.pone.0024646
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Itakura T
中科院分区：
文献类型：
--
作者：
Kawabe-Yako R;Ii M;Masuo O;Asahara T;Itakura T
西洛他唑（CLZ）作为一种血管扩张抗血小板药物已被临床应用，并被证明抑制平滑肌细胞增殖和影响内皮细胞。然而，CLZ对再内皮化的影响，包括骨髓（BM）衍生的内皮祖细胞（EPC）的贡献尚不清楚。我们已经研究了CLZ可能加速EPCs再内皮化的假设。在雄性Sprague-Dawley大鼠中进行球囊颈动脉剥脱。CLZ组于颈动脉损伤前2周开始给予CLZ混合饲料喂养。对照组喂普通饲料。CLZ组术后2周再内皮化明显加快，术后4周新生内膜形成明显减少。CLZ还增加了整个时间过程中循环EPCs的数量。我们通过从Tie 2/lacZ小鼠骨髓移植到裸大鼠骨髓中来检测骨髓来源的EPCs对再内皮化的贡献。术后2周CLZ组损伤动脉管腔表面Tie 2调控的X-gal阳性细胞数较对照组增多。在体外，CLZ可增强大鼠骨髓来源的EPCs的增殖、粘附和迁移活性，并通过实时定量RT-PCR评估粘附分子整合素αvβ3、趋化因子受体CXCR 4和生长因子VEGF的mRNA上调促进其分化。此外，CLZ显著增加血管损伤后EPCs中CXCR 4受体配体SDF-1α的表达。在大鼠颈动脉球囊损伤模型中，CLZ促进EPC从BM动员和EPC募集到动脉损伤部位，从而抑制新生内膜形成，加速EPC和预先存在的内皮细胞的再内皮化。CLZ不仅是一种抗血小板药物，而且是一种有前途的内皮再生工具，这是预防动脉粥样硬化或血管介入后再狭窄的关键事件。
Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
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Dimmeler, S;Aicher, A;Zeiher, AM
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Douglas, JS;Holmes, DR;Weintraub, WS
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Weintraub, WS
CXCR4基因转移有助于内皮祖细胞的体内再内皮化能力
影响因子：
10.8
作者：
Chen, Long;Wu, Fang;Tao, Jun
通讯作者：
Tao, Jun
影响因子：
82.9
作者：
Aicher, A;Heeschen, C;Dimmeler, S
通讯作者：
Dimmeler, S