Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression.
Advanced glycation end product (AGE)-their receptor (RAGE) and angiotensin II (AII) are implicated in diabetic retinopathy. However, a crosstalk between the two is not fully understood. In vivo, AGE injection stimulated RAGE expression in the eye of spontaneously hypertensive rats, which was blocked by an AII-type 1 receptor blocker, telmisartan. In vitro, AII-type 1 receptor-mediated reactive oxygen species generation elicited RAGE gene expression in pericytes through NF-kappaB activation. Further, AII augmented AGE-induced pericyte apoptosis, the earliest hallmark of diabetic retinopathy. Our present study may implicate a crosstalk between AGE-RAGE system and AII in diabetic retinopathy.
Yamagishi
Sho-Ichi
S
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Takeuchi
Masayoshi
M
Matsui
Takanori
T
Nakamura
Kazuo
K
Imaizumi
Tsutomu
T
Inoue
Hiroyoshi
H
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D011971:Receptors, Immunologic; D012160:Retina / Q000166:cytology; D000077333:Telmisartan; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D044140:Receptor, Angiotensin, Type 1; D011971:Receptors, Immunologic; D000804:Angiotensin II; D000077333:Telmisartan