Roles of the AGE-RAGE system in vascular injury in diabetes

Yasuhiko Yamamoto, Sho Ichi Yamagishi, Hideto Yonekura, Toshio Doi, Hiroko Tsuji, Ichiro Kato, Shin Takasawa, Hiroshi Okamoto, Joynal Abedin, Nobushige Tanaka, Shigeru Sakurai, Hideyuki Migita, Hiroyuki Unoki, Hua Wang, Takahiro Zenda, Ping Sheng Wu, Yasunori Segawa, Tomomi Higashide, Kazuo Kawasaki, Hiroshi Yamamoto

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)


This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy, AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2000


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