PMID- 18287887
OWN - NLM
STAT- MEDLINE
DCOM- 20080709
LR  - 20171116
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 51
IP  - 2
DP  - 2008 Feb
TI  - Molecular mechanisms of felodipine suppressing atherosclerosis in 
      high-cholesterol-diet apolipoprotein E-knockout mice.
PG  - 188-95
LID - 10.1097/FJC.0b013e31815f2bce [doi]
AB  - Oxidative stress and inflammation processes are key components of 
      atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. 
      Evidence has revealed that calcium-channel blockers (CCB) could retard 
      atherogenesis, but the exact mechanisms have not been fully elucidated. The 
      present study was undertaken to investigate the potential effects and molecular 
      mechanisms of the CCB felodipine on the process of atherosclerosis in 
      high-cholesterol-diet (HCD) apolipoprotein E-knockout (ApoE KO) mice. Adult male 
      ApoE KO mice were given a normal diet (ND) or HCD and were randomized to no 
      treatment or felodipine (5 mg / kg per day for 12 weeks). The ApoE KO mice with 
      HCD were associated with a marked increase in plasma lipid levels, 
      atherosclerotic lesion area, and the expressions of NADPH oxidase subunits (p47 
      and Rac-1), nuclear factor-kappaB (NF-kappaB) in nucleus, phosphor-inhibitors of 
      kappaB (p-IkappaB), tumor necrosis-alpha (TNF-alpha), monocyte chemoattractant 
      protein-1 (MCP-1), and vascular cell-adhesion molecule-1 (VCAM-1). These changes 
      were suppressed in mice that were treated with felodipine (5 mg/kg per day for 12 
      weeks) concomitant with HCD administration, with no significant change in 
      systolic blood pressure and plasma lipid levels. The results suggest that 
      felodipine can attenuate atherosclerosis, and this effect is partly related to 
      inhibition of oxidative stress and inflammatory signal-transduction pathways, 
      which lead to decreases in the expression of inflammatory cytokines.
FAU - Yao, Rui
AU  - Yao R
AD  - Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, 
      Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 
      China.
FAU - Cheng, Xiang
AU  - Cheng X
FAU - Liao, Yu-Hua
AU  - Liao YH
FAU - Chen, Yong
AU  - Chen Y
FAU - Xie, Jiang-Jiao
AU  - Xie JJ
FAU - Yu, Xian
AU  - Yu X
FAU - Ding, Ying-Jun
AU  - Ding YJ
FAU - Tang, Ting-Ting
AU  - Tang TT
LA  - eng
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 (Apolipoproteins E)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Lipids)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - OL961R6O2C (Felodipine)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*genetics
MH  - Atherosclerosis/*drug therapy/etiology/metabolism
MH  - Blood Pressure/drug effects
MH  - Calcium Channel Blockers/pharmacology/*therapeutic use
MH  - Chemokine CCL2/metabolism
MH  - Cholesterol, Dietary/*administration & dosage
MH  - Diet, Atherogenic
MH  - Felodipine/pharmacology/*therapeutic use
MH  - Lipids/blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/drug effects
MH  - Random Allocation
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2008/02/22 09:00
MHDA- 2008/07/10 09:00
CRDT- 2008/02/22 09:00
PHST- 2008/02/22 09:00 [pubmed]
PHST- 2008/07/10 09:00 [medline]
PHST- 2008/02/22 09:00 [entrez]
AID - 00005344-200802000-00011 [pii]
AID - 10.1097/FJC.0b013e31815f2bce [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2008 Feb;51(2):188-95. doi: 10.1097/FJC.0b013e31815f2bce.