PMID- 15071361
OWN - NLM
STAT- MEDLINE
DCOM- 20041222
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 43
IP  - 5
DP  - 2004 May
TI  - Azelnidipine, a newly developed long-acting calcium antagonist, inhibits tumor 
      necrosis factor-alpha-induced interleukin-8 expression in endothelial cells 
      through its anti-oxidative properties.
PG  - 724-30
AB  - Interleukin-8 (IL-8), a member of CXC chemokine family, has been found to play an 
      important role in the pathogenesis of atherosclerosis. Tumor necrosis 
      factor-alpha (TNF-alpha) is involved in the development and progression of 
      atherosclerosis as well. In this study, we investigated whether and how 
      azelnidipine, a newly developed long-acting calcium antagonist, could inhibit 
      TNF-alpha-induced IL-8 expression in human umbilical vein endothelial cells 
      (HUVEC). TNF-alpha significantly increased intracellular reactive oxygen species 
      (ROS) generation in HUVEC, which was completely blocked by azelnidipine or 
      apocynin, an inhibitor of NADPH oxidase. Azelnidipine also completely prevented 
      TNF-alpha-induced increase in NADPH oxidase activity in HUVEC. Further, 
      azelnidipine was found to significantly inhibit activator protein-1 (AP-1) 
      promoter activity and IL-8 expression in TNF-alpha-exposed HUVEC. An inhibitor of 
      AP-1, curcumin, or an anti-oxidant, N-acetylcysteine, also inhibited the 
      TNF-alpha-induced IL-8 expression in HUVEC. These results demonstrated that 
      azelnidipine inhibited TNF-alpha-induced IL-8 expression in HUVEC by blocking 
      NADPH oxidase-mediated ROS generation and subsequent AP-1 activation. Our present 
      study suggests that azelnidipine may play a protective role in the development 
      and progression of atherosclerosis through its anti-oxidative properties.
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
AD  - Department of Internal Medicine III, Kurume University School of Medicine, 
      Kurume, Japan. shoichi@med.kurume-u.ac.jp
FAU - Inagaki, Yosuke
AU  - Inagaki Y
FAU - Nakamura, Kazuo
AU  - Nakamura K
FAU - Imaizumi, Tsutomu
AU  - Imaizumi T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Antioxidants)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 0 (Interleukin-8)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1J444QC288 (Amlodipine)
RN  - 5GZ3E0L9ZU (Azetidinecarboxylic Acid)
RN  - PV23P19YUG (azelnidipine)
SB  - IM
MH  - Amlodipine/pharmacology
MH  - Antioxidants/*pharmacology
MH  - Azetidinecarboxylic Acid/*analogs & derivatives/*pharmacology
MH  - Calcium Channel Blockers/*pharmacology
MH  - Dihydropyridines/*pharmacology
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-8/*biosynthesis
MH  - Radioligand Assay
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factor AP-1/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology/physiology
MH  - Umbilical Veins/enzymology
EDAT- 2004/04/09 05:00
MHDA- 2004/12/23 09:00
CRDT- 2004/04/09 05:00
PHST- 2004/04/09 05:00 [pubmed]
PHST- 2004/12/23 09:00 [medline]
PHST- 2004/04/09 05:00 [entrez]
AID - 00005344-200405000-00016 [pii]
AID - 10.1097/00005344-200405000-00016 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2004 May;43(5):724-30. doi: 
      10.1097/00005344-200405000-00016.