Roles of the AGE-RAGE system in vascular injury in diabetes.
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.
Yamamoto
Y
Y
Department of Biochemistry, Kanazawa University School of Medicine, Japan.
Yamagishi
S
S
Yonekura
H
H
Doi
T
T
Tsuji
H
H
Kato
I
I
Takasawa
S
S
Okamoto
H
H
Abedin
J
J
Tanaka
N
N
Sakurai
S
S
Migita
H
H
Unoki
H
H
Wang
H
H
Zenda
T
T
Wu
P S
PS
Segawa
Y
Y
Higashide
T
T
Kawasaki
K
K
Yamamoto
H
H
D000818:Animals; D002417:Cattle; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000503:physiopathology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D017127:Glycation End Products, Advanced; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor