Combined dermatan sulfate and endothelial progenitor cell treatment: action on the initial inflammatory response after arterial injury in C57BL/6 mice.
OBJECTIVE
Dermatan sulfate (DS), an anticoagulant and antithrombotic glycosaminoglycan, also has anti-inflammatory activity. In this study, we investigated the effect of DS treatment in the presence or absence of bone marrow mononuclear cells (MNCs) or endothelial progenitor cells (EPCs) in the vascular response to carotid artery lesion in C57BL6 mice.


METHODS
Thrombus formation, the expression of adhesion molecules and factors involved in vascular remodeling, inflammation or vascular tone were analyzed by histologic examination, Western blotting and enzyme-linked immunoassay 1 and 3 days after vascular injury.


RESULTS
DS injections prevented thrombus formation and decreased P-selectin expression after 3 days of the injury. DS treatment also increased plasma SDF-1 levels but failed to rescue endothelial nitric oxide synthase (eNOS) expression, which is responsible for vascular tone. Treatment with MNCs alone failed to prevent thrombus formation 1 day after injury and increased intercellular adhesion molecule-1 expression, likely because of the inflammatory nature of these cells. Treatment with EPCs with DS was the most efficient among all therapies studied. Dual administration of EPCs and DS promoted an increase in the expression of adhesion molecules and, at the same time, induced a higher expression of eNOS at the injury site. Furthermore, it stimulated an elevated number of EPCs to migrate and adhere to the vascular wall.


CONCLUSIONS
Simultaneous treatment with EPCs and DS increased the expression of adhesion molecules, prevented thrombosis, rescued the expression of eNOS and increased migration of EPCs to the site of injury, thereby affecting thrombus remodeling and inflammation and can be involved in vessel hemostasis.
Departments of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Juliana A P
JA
Godoy
Departments of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Giane D
GD
Carneiro
Departments of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Micheli S
MS
Sielski
Departments of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Guilherme O
GO
Barbosa
Department of Biochemistry, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Claudio C
CC
Werneck
Departments of Structural and Functional Biology, Biology Institute, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. Electronic address: cvicente@unicamp.br.
Cristina P
CP
Vicente
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D003131:Combined Modality Therapy; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D066026:Endothelial Progenitor Cells / Q000637:transplantation*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D019007:P-Selectin / Q000096:biosynthesis; D013927:Thrombosis / Q000517:prevention & control*; D066253:Vascular Remodeling / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D005343:Fibrinolytic Agents; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D003871:Dermatan Sulfate; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
arteries; dermatan sulfate; inflammation; stem cells; vascular system injuries