Effect of Erythropoietin on Angiogenesis With the Increased Adhesion of Platelets to the Microvessels in the Hind-Limb Ischemia Model in Mice

Journal of Pharmacological Sciences

Shintaro Kato¹  Yukitoshi Satoh²  Toru Izumi⁶  Koji Eshima⁵  Hideki Amano²  Masataka Majima¹  Naoyoshi Aoyama¹  Hiroyuki Sakagami⁴  Yoshiya Ito³  Hideaki Tamaki⁴ 

[1] Department of Pharmacology, Kitasato University School of Medicine, Japan;Department of Thoracic Surgery, Kitasato University School of Medicine, Japan;Department of Surgery, Kitasato University School of Medicine, Japan;Department of Anatomy, Kitasato University School of Medicine, Japan;Department of Immunology, Kitasato University School of Medicine, Japan;Department of Cardio-angiology, Kitasato University School of Medicine, Japan

关键词: angiogenesis;    erythropoietin;    intravital microscopy;    platelet;    P-selectin;   

DOI  :  10.1254/jphs.09262FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(25)Cited-By(19)Erythropoietin (EPO) has been shown to enhance angiogenesis, but its precise mechanisms of enhancement during ischemia are not fully elucidated. We examined the effect of EPO on blood flow recovery from acute hind-limb ischemia induced by ligation of the femoral artery in male C57Bl/6 mice. The density of microvessels with platelet adhesion in ischemic tissues was assessed by intravital microscopy. Treatment with EPO (100 and 1000 IU/kg, i.p.) restored blood flow in a dose-dependent manner and increased plasma levels of soluble-P-selectin, vascular endothelial growth factor (VEGF), and stromal cell–derived factor (SDF-1). Flow cytometric analysis revealed increased P-selectin expression on platelets in EPO-treated mice compared to PBS-treated mice. Intravital microscopic studies showed that EPO increased density of microvessels with platelet adhesion selectively in the ischemic tissues. Neutralizing antibody against P-selectin reduced the density of microvessels with platelet adhesion enhanced with EPO and impaired blood flow recovery with reductions in VEGF and SDF-1 levels. These results suggest that EPO administration enhances recovery from hind-limb ischemia, and platelet adhesion to the microvessels is a key event to enhance the angiogenesis in the ischemic tissues.

【 授权许可】

Unknown