TY - JOUR
T1 - Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro
AU - Okamoto, Tamami
AU - Yamagishi, Sho ichi
AU - Inagaki, Yosuke
AU - Amano, Shinjiro
AU - Takeuchi, Masayoshi
AU - Kikuchi, Seiji
AU - Ohno, Shigeaki
AU - Yoshimura, Akihiko
N1 - Funding Information:
This work was supported in part by Grants of Venture Research and Development Centers from the Ministry of Education, Culture, Sports, Science and Technology, Japan (S.Y.), the Suzuken Memorial Foundation, Japan (S.Y.), and the Mochida Memorial Foundation for Medical and Pharmaceutical Research, Japan (S.Y.).
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Diabetic retinopathy
KW - Glycation
KW - Incadronate disodium
KW - VEGF
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U2 - 10.1016/S0006-291X(02)02218-0
DO - 10.1016/S0006-291X(02)02218-0
M3 - Article
C2 - 12237136
AN - SCOPUS:0036399062
SN - 0006-291X
VL - 297
SP - 419
EP - 424
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
