Administration of recombinant P-selectin glycoprotein ligand Fc fusion protein suppresses inflammation and neointimal formation in Zucker diabetic rat model.
OBJECTIVE
P-selectin-mediated leukocyte-endothelium and leukocyte-platelet interaction has been reported after vascular injury and has been correlated with neointimal hyperplasia, but its role in neointimal formation after arterial injury in diabetes has not been described.


RESULTS
Using a Zucker diabetic rat balloon injury model, we examined the role of P-selectin in the vascular inflammatory process and neointimal formation after balloon injury. Immunohistochemistry revealed that P-selectin was intensely expressed and that CD45-positive leukocyte infiltration was significantly increased after arterial injury. A single preprocedural intravenous administration of a recombinant P-selectin-soluble glycoprotein ligand-Ig inhibited CD45-positive leukocyte accumulation and suppressed neointimal formation in the Zucker diabetic rat model.


CONCLUSIONS
These results suggest that reduction of P-selectin-mediated leukocyte activation with the use of recombinant P-selectin-soluble glycoprotein ligand-Ig decreases the inflammatory response and limits neointimal formation after balloon injury in diabetes.
Zhou
Zhongmin
Z
Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Penn
Marc S
MS
Forudi
Farhad
F
Zhou
Xiaorong
X
Tarakji
Khaldoun
K
Topol
Eric J
EJ
Lincoff
A Michael
AM
Wang
Kai
K
D000818:Animals; D016466:CHO Cells; D020212:Carotid Artery Injuries / Q000150:complications / Q000209:etiology; D016893:Carotid Stenosis / Q000209:etiology / Q000517:prevention & control; D002404:Catheterization / Q000009:adverse effects; D002460:Cell Line; D006224:Cricetinae; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000473:pathology; D004195:Disease Models, Animal; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019007:P-Selectin / Q000096:biosynthesis / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D055502:Secondary Prevention; D017539:Tunica Intima / Q000473:pathology*
D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D017493:Leukocyte Common Antigens