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 language | English |
|---|---|
| Pages (from-to) | 886-891 |
| Number of pages | 6 |
| Journal | Journal of International Medical Research |
| Volume | 35 |
| Issue number | 6 |
| Publication status | Published - 2007 Nov |
| Externally published | Yes |
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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
- Medicine(all)
Cite this
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. / Matsui, T.; Yamagishi, Sho Ichi; Nakamura, K.; Inoue, Hiroyoshi.
In: Journal of International Medical Research, Vol. 35, No. 6, 11.2007, p. 886-891.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Matsui, T.
AU - Yamagishi, Sho Ichi
AU - Nakamura, K.
AU - Inoue, Hiroyoshi
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Bay w 9798
KW - Dihydropyridines
KW - Human umbilical vein endothelial cells (HUVECs)
KW - Nifedipine
KW - Oxidative stress
KW - Tumour necrosis factor-α (TNF-α)
KW - Vascular cell adhesion molecule-1 (VCAM-1)
UR - http://www.scopus.com/inward/record.url?scp=36949040856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36949040856&partnerID=8YFLogxK
M3 - Article
C2 - 18084847
AN - SCOPUS:36949040856
VL - 35
SP - 886
EP - 891
JO - Journal of International Medical Research
JF - Journal of International Medical Research
SN - 0300-0605
IS - 6
ER -