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The role of the fibrocyte in intimal hyperplasia

Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow‐derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an ext...

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Published in:Journal of thrombosis and haemostasis 2006-05, Vol.4 (5), p.1125-1133
Main Authors: VARCOE, R. L., MIKHAIL, M., GUIFFRE, A. K., PENNINGS, G., VICARETTI, M., HAWTHORNE, W. J., FLETCHER, J. P., MEDBURY, H. J.
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Language:English
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Summary:Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow‐derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha‐smooth muscle actin (α‐SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and α‐SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and α‐SMA) and also to double stain for CD34 and α‐SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2006.01924.x