Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension.
There is a growing body of evidence that the advanced glycation end product (AGE)-their receptor (RAGE) system plays a central role in the pathogenesis of diabetic vascular complication. The renin-angiotensin system (RAS) contributes to the development and progression of diabetic angiopathy as well. However, the cross-talk between the AGE-RAGE system and the RAS is not fully understood. In this study, we examined the role of angiotensin II (Ang II) type 1 receptor system for RAGE expression in cultured endothelial cells (ECs) and in patients with essential hypertension. Ang II up-regulated RAGE mRNA levels of microvascular ECs and subsequently increased the soluble form of RAGE (sRAGE) expression in the medium of ECs, both of which were completely blocked by telmisartan, a commercially available Ang II type 1 receptor antagonist. Furthermore, telmisartan was found to decrease serum levels of sRAGE in patients with essential hypertension. These results demonstrate that sRAGE is released from the cell surface of Ang-II-exposed ECs. Our present study indicates that a cross-talk exists between the AGE-RAGE system and the RAS and suggests that serum levels of sRAGE may reflect endothelial RAGE expression.
Nakamura
Kazuo
K
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Yamagishi
Sho-Ichi
S
Nakamura
Yayoi
Y
Takenaka
Katsuhiko
K
Matsui
Takanori
T
Jinnouchi
Yuko
Y
Imaizumi
Tsutomu
T
D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D003324:Coronary Artery Disease / Q000097:blood / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077333:Telmisartan; D013997:Time Factors; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D017931:DNA Primers; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000804:Angiotensin II; D000077333:Telmisartan