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Circulating endothelial progenitor cells do not contribute to regeneration of endothelium after murine arterial injury
Aims Endothelial regeneration after vascular injury, including percutaneous coronary intervention, is essential for vascular homeostasis and inhibition of neointima formation. Circulating endothelial progenitor cells (EPCs) have been implicated to contribute by homing and differentiating into endoth...
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Published in: | Cardiovascular research 2012-02, Vol.93 (2), p.223-231 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Aims
Endothelial regeneration after vascular injury, including percutaneous coronary intervention, is essential for vascular homeostasis and inhibition of neointima formation. Circulating endothelial progenitor cells (EPCs) have been implicated to contribute by homing and differentiating into endothelial cells (ECs). We tested this theory in a murine arterial injury model using carotid artery transplants and fluorescent reporter mice.
Methods and results
Wire-injured carotid artery segments from wild-type mice were transplanted into TIE2-GFP transgenic mice expressing green fluorescent protein (GFP) in ECs. We found that the endothelium regenerated with GFP+ ECs as a function of time, evolving from the anastomosis sites towards the centre of the transplant. A migration front of ECs at Day 7 was verified by scanning electron microscopy and by bright-field microscopy using recipient TIE2-lacZ mice with endothelial β-galactosidase expression. These experiments indicated migration of flanking ECs rather than homing of circulating cells as the underlying mechanism. To confirm this, we interposed non-injured wild-type carotid artery segments between the denuded transplant and the TIE2-GFP recipient mouse. Among 1186 ECs identified in re-endothelialized transplants (n= 5) by staining for von Willebrand Factor or vascular endothelial-cadherin, we did not find any blood-derived (GFP+) cells.
Conclusion
Endothelial regeneration after vascular injury did not involve circulating EPCs but was mediated solely by migration of ECs from the adjacent healthy endothelium. |
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ISSN: | 0008-6363 1755-3245 |
DOI: | 10.1093/cvr/cvr278 |