Ischemia-induced angiogenesis: role of inflammatory response

Abstract: P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-se-lectin mediates the tethering and rolling of leuko-cytes along the endothelium, an early step of leu-kocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogene-sis, 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 isch-emia, 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 re-vealed the number of infiltrated leukocytes ex-pressing 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 be-come one possible target molecule for modulating inflammatory angiogenesis. J. Leukoc. Biol. 79