PMID- 25110549
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2014
DP  - 2014
TI  - Atorvastatin represses the angiotensin 2-induced oxidative stress and 
      inflammatory response in dendritic cells via the PI3K/Akt/Nrf 2 pathway.
PG  - 148798
LID - 10.1155/2014/148798 [doi]
LID - 148798
AB  - Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play 
      a complex role in both the initiation and progression of atherosclerosis. We 
      tested the hypothesis that the anti-inflammatory and antioxidant effects of 
      atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein 
      kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 
      (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the 
      inflammatory and oxidative stress responses. This study showed that angiotensin 2 
      (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 
      expression, and increased the secretion of IL-12p70, IL-6, and TNF-alpha. These 
      effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of 
      reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their 
      initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 
      via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the 
      cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a 
      process that was reversed by the PI3K inhibitor LY294002. Therefore, the 
      regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in 
      the regulation of the statin-mediated antioxidant and anti-inflammatory responses 
      in DCs.
FAU - Ma, Yuanji
AU  - Ma Y
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, 180 Fenglin Road, Shanghai 200032, China ; Institute of Biomedical 
      Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
FAU - Chen, Zhaoyang
AU  - Chen Z
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, 180 Fenglin Road, Shanghai 200032, China ; Institute of Biomedical 
      Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
FAU - Zou, Yunzeng
AU  - Zou Y
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, 180 Fenglin Road, Shanghai 200032, China ; Institute of Biomedical 
      Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
FAU - Ge, Junbo
AU  - Ge J
AD  - Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan 
      University, 180 Fenglin Road, Shanghai 200032, China ; Institute of Biomedical 
      Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140703
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Heptanoic Acids)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Pyrroles)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Animals
MH  - Anticholesteremic Agents/*pharmacology
MH  - Atorvastatin
MH  - Bone Marrow Cells/cytology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dendritic Cells/cytology/*drug effects/metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrroles/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - Superoxide Dismutase/metabolism
MH  - T-Lymphocytes/cytology/immunology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4106155
EDAT- 2014/08/12 06:00
MHDA- 2015/03/31 06:00
PMCR- 2014/07/03
CRDT- 2014/08/12 06:00
PHST- 2014/03/12 00:00 [received]
PHST- 2014/06/11 00:00 [revised]
PHST- 2014/06/11 00:00 [accepted]
PHST- 2014/08/12 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2014/07/03 00:00 [pmc-release]
AID - 10.1155/2014/148798 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2014;2014:148798. doi: 10.1155/2014/148798. Epub 2014 Jul 
      3.