Bay w 9798, a dihydropyridine structurally related to nifedipine with no calcium channel-blocking properties, inhibits tumour necrosis factor-α-induced vascular cell adhesion molecule-1 expression in endothelial cells by suppressing reactive oxygen species generation

T. Matsui, Sho Ichi Yamagishi, K. Nakamura, H. Inoue

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dihydropyridine-based calcium antagonists (DHPs) are widely used to treat hypertension. We have previously shown that nifedipine, one of the most popular DHPs, blocks tumour necrosis factor-α (TNF-α)-induced monocyte chemoattractant protein-1 as well as vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells by suppressing reactive oxygen species generation (ROS). The molecular mechanism is still to be elucidated, however, because endothelial cells do not possess voltage-operated L-type calcium channels. The aim of this study was to determine in TNF-α-exposed human umbilical vein endothelial cells (HUVECs) whether and how Bay w 9798, a dihydropyridine structurally related to nifedipine with no calcium antagonistic properties, may suppress VCAM-1 expression, a key molecule which mediates the adhesion of monocytes to vasculature in the early stages of atherosclerosis. In HUVECs, 10 ng/ml TNF-α for 4 h stimulated ROS generation and subsequently upregulated VCAM-1 mRNA levels, both of which were dose-dependently blocked by Bay w 9798. The results demonstrated that Bay w 9798 inhibited VCAM-1 expression in TNF-α-exposed cells by suppressing ROS generation. They suggest that the anti-inflammatory and anti-oxidative properties of nifedipine and Bay w 9798 may be ascribed to the dihydropyridine structure, which is common to both molecules and has no calcium antagonistic ability.

Original languageEnglish
Pages (from-to)886-891
Number of pages6
JournalJournal of International Medical Research
Volume35
Issue number6
DOIs
Publication statusPublished - 2007 Jan 1
Externally publishedYes

Keywords

  • Atherosclerosis
  • Bay w 9798
  • Dihydropyridines
  • Human umbilical vein endothelial cells (HUVECs)
  • Nifedipine
  • Oxidative stress
  • Tumour necrosis factor-α (TNF-α)
  • Vascular cell adhesion molecule-1 (VCAM-1)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

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