Nifedipine inhibits gene expression of receptor for advanced glycation end products (RAGE) in endothelial cells by suppressing reactive oxygen species generation.

Abstract

Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative stress generation in vascular wall cells through an interaction with their receptor (RAGE), thus playing an important role in vascular inflammation and altered gene expression of growth factors and cytokines. We have previously shown that nifedipine, one of the most popular dihydropyridine-based calcium antagonists, blocked tumor necrosis factor-alpha-induced monocyte chemoattractant protein-1 expression in endothelial cells (ECs) through its antioxidative properties. However, the effects of nifedipine on AGE-exposed ECs remain to be elucidated. In this study we investigated whether nifedipine could inhibit the AGE-induced reactive oxygen species (ROS) generation and subsequent RAGE gene expression in human umbilical vein endothelial cells (HUVEC). Nifedipine completely inhibited AGE-induced ROS generation in HUVEC. Furthermore, nifedipine was found to prevent up-regulation of RAGE mRNA levels in AGE-exposed HUVEC. These results demonstrate that nifedipine can inhibit RAGE overexpression in AGE-exposed ECs by suppressing ROS generation. Our present study suggests that nifedipine may have therapeutic potential in the treatment of patients with AGE-related disorders such as diabetic vascular complications.

• Authors: S Yamagishi, M Takeuchi
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 30 Issue 4 Pg. 169-75 ( 2004) ISSN: 0378-6501 [Print] Switzerland
• PMID: 15553663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycation End Products, Advanced
• RNA, Messenger
• Reactive Oxygen Species
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Serum Albumin
• Nifedipine

Topics

• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Gene Expression Regulation (drug effects, physiology)
• Glycation End Products, Advanced (adverse effects, antagonists & inhibitors, metabolism)
• Humans
• Nifedipine (pharmacology)
• RNA, Messenger (drug effects, metabolism)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (antagonists & inhibitors, drug effects, genetics)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Serum Albumin (metabolism, pharmacology)
• Umbilical Veins (drug effects, metabolism, pathology)