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Ischemia‐induced angiogenesis: role of inflammatory response mediated by P‐selectin
Author(s) -
Egami Kimiyasu,
Murohara Toyoaki,
Aoki Mika,
Matsuishi Toyojiro
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0805448
Subject(s) - angiogenesis , extravasation , ischemia , inflammation , hindlimb , p selectin , leukocyte extravasation , biology , immunology , endocrinology , pathology , medicine , cancer research , platelet , platelet activation
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 n 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.