PMID- 16940709
OWN - NLM
STAT- MEDLINE
DCOM- 20060919
LR  - 20171116
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 29
IP  - 6
DP  - 2006 Jun
TI  - Regression of atherosclerosis by amlodipine via anti-inflammatory and 
      anti-oxidative stress actions.
PG  - 457-66
AB  - We examined whether amlodipine, an L-type calcium channel blocker (CCB), has an 
      inhibitory effect on oxidative stress and inflammatory response, and thereby 
      atherosclerosis, in apolipoprotein E-deficient (ApoEKO) mice. Adult male ApoEKO 
      mice (6 weeks of age) were fed a high-cholesterol diet (HCD) for 8 or 10 weeks 
      with or without oral administration of amlodipine (3 mg/kg/day) for 10 weeks or 
      for only the last 2 weeks of the HCD. After HCD feeding, atherosclerotic lesion 
      formation, in situ superoxide production and nicotinamide-adenine dinucleotide 
      phosphate (NADPH) oxidase activity were evaluated in the proximal aorta. The 
      expressions of NADPH oxidase subunits (p47(phox) and rac-1), monocyte 
      chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), 
      and vascular cell adhesion molecule-1 (VCAM-1) were determined with 
      immunohistochemistry and quantitative real-time reverse-transcription polymerase 
      chain reaction. After 8 to 10 weeks of HCD administration to ApoEKO mice, marked 
      atherosclerotic lesion formation was observed in the proximal aorta. In the 
      atherosclerotic lesion, superoxide production, the expression of NADPH oxidase 
      subunits, and NADPH oxidase activity were enhanced, and the expressions of MCP-1, 
      ICAM-1, and VCAM-1 were increased. These changes were suppressed in mice that 
      were treated with amlodipine for 10 weeks concomitant with HCD administration, 
      with no significant change in blood pressure and plasma cholesterol level. We 
      also observed that treatment with amlodipine for only the last 2 weeks regressed 
      the atherosclerotic lesions with a decrease in oxidative stress and vascular 
      inflammation. Inhibition of the atherosclerotic lesion area and lipid area in the 
      proximal aorta by amlodipine was correlated with its inhibitory actions on 
      oxidative stress, inflammation and the production of adhesive molecules. These 
      results suggest that amlodipine not only inhibits atherosclerotic lesion 
      formation, but also regresses atherosclerosis, and that these effects are at 
      least partly due to inhibition of oxidative stress and inflammatory response.
FAU - Yoshii, Toyofumi
AU  - Yoshii T
AD  - Second Department of Internal Medicine, Ehime University School of Medicine, 
      hitsukawa, Tohon, Japan.
FAU - Iwai, Masaru
AU  - Iwai M
FAU - Li, Zhen
AU  - Li Z
FAU - Chen, Rui
AU  - Chen R
FAU - Ide, Ayumi
AU  - Ide A
FAU - Fukunaga, Shiori
AU  - Fukunaga S
FAU - Oshita, Akira
AU  - Oshita A
FAU - Mogi, Masaki
AU  - Mogi M
FAU - Higaki, Jitsuo
AU  - Higaki J
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 11062-77-4 (Superoxides)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 1J444QC288 (Amlodipine)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Amlodipine/pharmacology/*therapeutic use
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Antioxidants/pharmacology/*therapeutic use
MH  - Apolipoproteins E/genetics/physiology
MH  - Atherosclerosis/*drug therapy/genetics/pathology/physiopathology
MH  - Calcium Channel Blockers/pharmacology/*therapeutic use
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cholesterol, Dietary/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Inflammation/drug therapy/metabolism/physiopathology
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - NADPH Oxidases/genetics/metabolism
MH  - Oxidative Stress/*drug effects/physiology
MH  - Superoxides/metabolism
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
EDAT- 2006/08/31 09:00
MHDA- 2006/09/20 09:00
CRDT- 2006/08/31 09:00
PHST- 2006/08/31 09:00 [pubmed]
PHST- 2006/09/20 09:00 [medline]
PHST- 2006/08/31 09:00 [entrez]
AID - JST.JSTAGE/hypres/29.457 [pii]
AID - 10.1291/hypres.29.457 [doi]
PST - ppublish
SO  - Hypertens Res. 2006 Jun;29(6):457-66. doi: 10.1291/hypres.29.457.