Advanced glycation end products induce angiogenesis in vivo.
Advanced glycation end products (AGEs) have been thought to participate in diabetic microangiopathy. However, the effects of AGEs on angiogenesis have so far been mainly examined either in vitro or by using cultured cells. In the present study, we have analyzed whether AGEs induce angiogenesis in vivo by using the chorioallantoic membrane (CAM) assay. The CAM assay was carried out in embryonated hen eggs to determine the effects of AGEs. Following generation of AGEs based on bovine serum albumin (BSA), either AGE-BSA or nonglycated BSA was administered to the CAM and their effects on angiogenesis were assessed, together with an inhibitory effect of an anti-AGE antibody against AGE-BSA-induced angiogenesis. The histological features of AGE-induced vascular lumens were examined by immunohistochemical analysis for Factor VIII and smooth muscle alpha-actin. AGE-BSA induced angiogenesis in CAM in a dose- and time-dependent manner. AGE-induced angiogenesis on CAM was neutralized by the anti-AGE antibody. Immunohistochemical analysis demonstrated that AGE-induced vascular lumens were devoid of pericytes. Our data demonstrated that AGEs are an angiogenetic factor and that our system of AGE-induced abnormal vessels in CAMs is useful in further investigations of the mechanism of diabetic retinal angiogenesis and can also be used to provide a therapeutic model for diabetic angiopathy.
Okamoto
Tamami
T
Laboratory of Molecular & Cellular Pathology, Hokkaido University School of Medicine, N 15, W7, Kita-ku, Sapporo, 060-8638, Japan.
Tanaka
Shinya
S
Stan
Alex C
AC
Koike
Takao
T
Kase
Manabu
M
Makita
Zenji
Z
Sawa
Hirofumi
H
Nagashima
Kazuo
K
D000818:Animals; D002642:Chick Embryo; D002823:Chorion / Q000378:metabolism; D048909:Diabetes Complications; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000494:pharmacology; D017709:Fractals; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008222:Lymphokines / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D017127:Glycation End Products, Advanced; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors