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

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume297
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Angiogenesis
  • Diabetic retinopathy
  • Glycation
  • Incadronate disodium
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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