Dermatan sulfate and bone marrow mononuclear cells used as a new therapeutic strategy after arterial injury in mice.
OBJECTIVE
Previously, we have demonstrated that administration of dermatan sulfate (DS) suppresses neointima formation in the mouse carotid artery by activating heparin co-factor II. A similar suppressive effect was observed by increasing the number of progenitor cells in circulation. In this study, we investigated the combination of DS and bone marrow mononuclear cells (MNC), which includes potential endothelial progenitors, in neointima formation after arterial injury.


METHODS
Arterial injury was induced by mechanical dilation of the left common carotid artery. We analyzed the extension of endothelial lesion, thrombus formation, P-selectin expression and CD45(+) cell accumulation 1 and 3 days post-injury, and neointima formation 21 days post-injury. Animals were injected with MNC with or without DS during the first 48 h after injury.


RESULTS
The extension of endothelial lesion was similar in all groups 1 day after surgery; however, in injured animals treated with MNC and DS the endothelium recovery seemed to be more efficient 21 days after lesion. Treatment with DS inhibited thrombosis, decreased CD45(+) cell accumulation and P-selectin expression at the site of injury, and reduced the neointimal area by 56%. Treatment with MNC reduced the neointimal area by 54%. The combination of DS and MNC reduced neointima formation by more than 91%. In addition, DS promoted a greater accumulation of MNC at the site of injury.


CONCLUSIONS
DS inhibits the initial thrombotic and inflammatory processes after arterial injury and promotes migration of MNC to the site of the lesion, where they may assist in the recovery of the injured endothelium.
Department of Anatomy, Cellular Biology, Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), São Paulo, Brazil.
Juliana A P
JA
Godoy
Daniel B
DB
Block
Douglas M
DM
Tollefsen
Claudio C
CC
Werneck
Cristina P
CP
Vicente
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058426:Neointima / Q000517:prevention & control* / Q000628:therapy*; D019007:P-Selectin / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control / Q000628:therapy
D000925:Anticoagulants; D019007:P-Selectin; D003871:Dermatan Sulfate; D017493:Leukocyte Common Antigens