| Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. | |
MedLine Citation:
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PMID: 20644015 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-1alpha. 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. |
Authors:
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Sebastian F Mause; Elisabeth Ritzel; Elisa A Liehn; Mihail Hristov; Kiril Bidzhekov; Gerhard Müller-Newen; Oliver Soehnlein; Christian Weber |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-19 |
Journal Detail:
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Title: Circulation Volume: 122 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-03 Completed Date: 2010-09-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 495-506 Citation Subset: AIM; IM |
Affiliation:
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Medical Faculty, Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Blood Platelets / cytology, physiology* Carotid Arteries / pathology, physiology Carotid Artery Injuries / pathology, physiopathology* Cell Communication / physiology Cell Differentiation / physiology Cell Division / physiology Cell Movement / physiology Cell-Derived Microparticles / physiology* Cells, Cultured Chemokine CXCL12 / metabolism Cytoskeleton / physiology Disease Models, Animal Endothelial Cells / cytology, physiology* Flow Cytometry Humans Mice Mice, Inbred C57BL Mice, Nude Neovascularization, Physiologic / physiology* Receptors, CXCR4 / metabolism Regeneration / physiology Umbilical Veins / cytology |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/CXCL12 protein, human; 0/CXCR4 protein, human; 0/Chemokine CXCL12; 0/Receptors, CXCR4 |
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