Blockade of angiotensin II receptors reduces the expression of receptors for advanced glycation end products in human endothelial cells.

Abstract

OBJECTIVE:

Receptors for advanced glycation end products (RAGEs) play crucial roles in atherogenesis. Because tumor necrosis factor alpha (TNFalpha) is expressed and upregulates RAGE expression in atherosclerotic lesions, the TNFalpha-RAGE interaction might be involved in the inflammatory process of atherogenesis. On the other hand, an angiotensin II type-1 receptor blocker (ARB), widely used as an antihypertensive drug, has been reported to have also antiatherosclerotic effects. Thus we investigated whether an ARB exerts antiatherosclerotic effects via inhibiting the TNFalpha-RAGE interaction.

METHODS AND RESULTS:

Stimulation of human endothelial cells with candesartan as well as olmesartan decreased TNFalpha-induced RAGE expression in both mRNA and protein levels along with the decrease in the activity of nuclear factor kappaB and the expression of inflammatory mediators such as vascular cell adhesion molecule (VCAM)-1. Both candesartan and olmesartan inhibited the binding of nuclear factor kappaB to the RAGE gene promoter. Furthermore, gene silencing of RAGE by RNA interference decreased the expression of TNFalpha-induced VCAM-1 in both mRNA and protein levels.

CONCLUSIONS:

RAGE contributes at least partially to the TNFalpha-induced VCAM-1 expression in both mRNA and protein levels. Blockade of angiotensin II receptors might exert antiatherosclerotic effects via reducing TNFalpha-RAGE interaction.

• Authors: Masashi Fujita, Hiroko Okuda, Osamu Tsukamoto, Yoshihiro Asano, Yulin Liao Akio Hirata, Jiyoong Kim, Takeshi Miyatsuka, Seiji Takashima, Tetsuo Minamino, Hitonobu Tomoike, Masafumi Kitakaze
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 26 Issue 10 Pg. e138-42 (Oct 2006) ISSN: 1524-4636 [Electronic] United States
• PMID: 16888237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• Imidazoles
• NF-kappa B
• RNA, Messenger
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Tetrazoles
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• olmesartan
• candesartan

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Gene Silencing
• Humans
• Imidazoles (pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Promoter Regions, Genetic
• RNA Interference
• RNA, Messenger (antagonists & inhibitors, metabolism)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (antagonists & inhibitors, genetics)
• Tetrazoles (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• Umbilical Veins (cytology)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)