Platelet Microparticles Enhance the Vasoregenerative Potential of Angiogenic Early Outgrowth Cells After Vascular Injury
Platelet Microparticles Enhance the Vasoregenerative Potential of Angiogenic Early Outgrowth Cells After Vascular Injury
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DOI：
10.1161/circulationaha.109.909473
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发表时间：
2010-08-03
期刊：
影响因子：
37.8
通讯作者：
Weber, Christian
中科院分区：
文献类型：
--
作者：
Mause, Sebastian F.;Ritzel, Elisabeth;Weber, Christian
背景-血管生成早期生长细胞（EOCs）已被报道有助于血管损伤后内皮再生和限制新生内膜形成。血管病理包括血小板活化和伴随的血小板微粒（PMP）的产生。我们假设，PMPs可能与EOCs在血管损伤的背景下，并调节其再生potential.Methods和结果，使用流式细胞术，共聚焦显微镜，扫描电子显微镜，我们证明了凝血酶/胶原诱导的PMPs的EOCs与随后的膜同化和掺入的结合。这种相互作用促进了EOCs的表型改变，增加了内皮细胞标志物的表达，并将趋化因子受体CXCR 4转移到对其配体CXCL 12/SDF-1 α的反应性增强的EOCs。此外，PMPs增强了EOCs与细胞外基质成分和受损血管壁的粘附，加速了EOCs的细胞骨架重组和迁移。PMPs诱导EOC分泌组向更促血管生成的方向变化，并放大了成熟内皮细胞对EOC介导的增殖、迁移和毛细血管形成的诱导作用。与未经处理的EOCs相比，注射PMP处理的EOCs导致加速再内皮化后动脉剥脱损伤在无胸腺裸鼠，而EOC介导的减少新生内膜形成保持不变。结论-我们的数据提供的证据表明，PMP可以提高EOCs的潜力，恢复血管损伤后的内皮完整性。其主要机制涉及EOC募集、迁移、分化和促血管生成因子释放的增强。（循环。2010; 122：495-506）。
Background-Angiogenic early outgrowth cells (EOCs) have been reported to contribute to endothelial regeneration and to limit neointima formation after vascular injury. Vascular pathologies comprise platelet activation and concomitant generation of platelet microparticles (PMPs). We hypothesized that PMPs may interact with EOCs in the context of vascular injury and modulate their regenerative potential.Methods and Results-Using flow cytometry, confocal microscopy, and scanning electron microscopy, we demonstrated the binding of thrombin/collagen-induced PMPs to EOCs with subsequent membrane assimilation and incorporation. This interaction promoted phenotypic alterations of EOCs with increased expression of endothelial cell markers and transfer of the chemokine receptor CXCR4 to EOCs with enhanced responsiveness to its ligand CXCL12/SDF-1 alpha. In addition, PMPs augmented the adhesion of EOCs to extracellular matrix components and to the injured vessel wall and accelerated cytoskeletal reorganization and migration of EOCs. PMPs induced changes in the EOC secretome toward a more proangiogenic profile and amplified the EOC-mediated induction of proliferation, migration, and capillary tube formation by mature endothelial cells. Compared with untreated EOCs, the injection of PMP-treated EOCs resulted in accelerated reendothelialization after arterial denudation injury in athymic nude mice, whereas the EOC-mediated reduction of neointima formation remained unchanged.Conclusions-Our data provide evidence that PMPs can boost the potential of EOCs to restore endothelial integrity after vascular injury. Major mechanisms involve the enhancement of EOC recruitment, migration, differentiation, and release of proangiogenic factors. (Circulation. 2010; 122: 495-506.)