Combined dermatan sulfate and endothelial progenitor cell treatment: action on the initial inflammatory response after arterial injury in C57BL/6 mice

Author(s)

Godoy, Juliana A. P. ^{[1, 2]} ; Carneiro, Giane D. ^{[1, 2]} ; Sielski, Micheli S. ^{[1, 2]} ; Barbosa, Guilherme O. ^{[1, 2]} ; Werneck, Claudio C. ^[3] ; Vicente, Cristina P. ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biol Struct, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Funct Biol, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biochem, Campinas, SP - Brazil

• Document type: Journal article
• Source: CYTOTHERAPY; v. 17, n. 10, p. 1447-1464, OCT 2015.
• Web of Science Citations: 4

Abstract

Background aims. 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. Discussion. 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. (AU)

• FAPESP's process: 10/01119-3 - Influence of glycosaminoglycans in the inflammatory process and cellular therapy using endothelial progenitor cells for recovery of mice arterial lesion.
• Grantee: Juliana Aparecida Preto de Godoy
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/23640-2 - The role of endothelial progenitor cells in arterial thrombosis and vascular remodeling observing the interference of dermatan sulfate, an antithrombotic glycosaminoglycan in this process
• Grantee: Cristina Pontes Vicente
• Support Opportunities: Regular Research Grants