Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin.
P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-selectin mediates the tethering and rolling of leukocytes along the endothelium, an early step of leukocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogenesis, little is known regarding the role of P-selectin in angiogenesis in the setting of tissue ischemia. We examined whether ischemia-induced angiogenesis is altered in P-selectin knockout (P-selectin(-/-)) mice. Angiogenesis was evaluated in a surgically induced hind-limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb LDBF ratio was persistently lower in P-selectin(-/-) mice compared with wild-type (WT) mice. CD was also significantly lower in P-selectin(-/-) mice than in WT mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory leukocytes infiltrated into the ischemic tissues in P-selectin(-/-) mice than in WT mice, and immunohistochemical analysis revealed the number of infiltrated leukocytes expressing vascular endothelial growth factor was also decreased in P-selectin(-/-) mice. P-selectin mRNA expression was augmented after hind-limb ischemia in WT mice. In conclusion, P-selectin may play an important role in ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell infiltration. P-selectin would become one possible target molecule for modulating inflammatory angiogenesis.
Egami
Kimiyasu
K
Department of Pediatrics, Kurume University School of Medicine, Japan.
Murohara
Toyoaki
T
Aoki
Mika
M
Matsuishi
Toyojiro
T
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D007511:Ischemia / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A