Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro

Tamami Okamoto, Sho ichi Yamagishi, Yosuke Inagaki, Shinjiro Amano, Masayoshi Takeuchi, Seiji Kikuchi, Shigeaki Ohno, Akihiko Yoshimura

研究成果: Article査読

59 被引用数 (Scopus)

抄録

We have previously shown that advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, induced angiogenesis through overgeneration of autocrine vascular endothelial growth factor (VEGF). In the present study, effects of incadronate disodium, a nitrogen-containing bisphosphonate on AGE-elicited angiogenesis in vitro, were studied. Incadronate disodium was found to completely inhibit AGE-induced increase in DNA synthesis as well as tube formation of human microvascular endothelial cells (EC). Furthermore, incadronate disodium significantly prevented transcriptional activation of nuclear factor-κB and activator protein-1 and the subsequent up-regulation of VEGF mRNA levels in AGE-exposed EC. Farnesyl pyrophosphate, but not geranylgeranyl pyrophosphate, was found to completely restore the anti-angiogenic effects of incadronate disodium on EC. These results suggest that incadronate disodium could block the AGE-signaling pathway in microvascular EC through inhibition of protein farnesylation. Incadronate disodium may be a promising remedy for treatment of patients with proliferative diabetic retinopathy.

本文言語English
ページ(範囲)419-424
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
297
2
DOI
出版ステータスPublished - 2002
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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