Table of Contents
ISRN Vascular Medicine
Volume 2013, Article ID 908108, 7 pages
http://dx.doi.org/10.1155/2013/908108
Research Article

Suppression of Receptor for Advanced Glycation End Products Improves Angiogenic Responses to Ischemia in Diabetic Mouse Hindlimb Ischemia Model

1Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Health System, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea
2Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea
3Yonsei Research Institute of Aging Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea
4Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea

Received 16 June 2013; Accepted 8 July 2013

Academic Editors: P. Schoenhagen, V. K. Sharma, S. Takebayashi, and Y. Tohno

Copyright © 2013 Bo Hyun Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The role of the receptor for advanced glycation end products (RAGE) for the impaired angiogenic response in diabetic patients is not well known. We investigated the impact of RAGE suppression by soluble RAGE (sRAGE) on the angiogenic response in a diabetic hindlimb ischemia mouse model. Materials and Methods. Hindlimb ischemia model was prepared by ligation of femoral artery in diabetic and nondiabetic mice. Ischemia-induced angiogenic response was evaluated by laser-Doppler perfusion imaging, muscle capillary density, and protein expression of vascular endothelial growth factor (VEGF) and high-mobility group box (HMGB)-1. Results. Diabetic mice showed attenuated recovery of ischemic limb perfusion on laser-Doppler perfusion imaging compared with nondiabetic mice. The treatment with sRAGE significantly improved blood flow in the ischemic limbs of diabetic mice. The expression levels of VEGF and HMGB-1 in the limb muscle tissues of diabetic mice were lower than in those of nondiabetic mice. The treatment with sRAGE significantly increased the VEGF and HMGB-1 protein expression in the ischemic limb muscle tissues in the diabetic mice. Conclusion. The suppression of RAGE by sRAGE administration improved angiogenic response to ischemia in diabetic mice and was associated with increased HMGB-1 and VEGF levels in muscle tissues.