PMID- 20074254
OWN - NLM
STAT- MEDLINE
DCOM- 20100311
LR  - 20181201
IS  - 1755-5922 (Electronic)
IS  - 1755-5914 (Linking)
VI  - 28
IP  - 1
DP  - 2010 Spring
TI  - Atorvastatin decreases C-reactive protein-induced inflammatory response in 
      pulmonary artery smooth muscle cells by inhibiting nuclear factor-kappaB pathway.
PG  - 8-14
LID - 10.1111/j.1755-5922.2009.00103.x [doi]
AB  - C-reactive protein (CRP) is well-known inflammatory marker, and recognized as a 
      risk predictor of pulmonary arterial diseases. Although statins have a beneficial 
      effect in animal models and patients with pulmonary arterial hypertension (PAH), 
      the underlying mechanisms of their actions have less been investigated. The aims 
      of this study was to examined the effects of CRP on expressions of interleukin-6 
      (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the possible 
      mechanisms of atorvastatin on CRP-induced IL-6 and MCP-1 production in cultured 
      human pulmonary artery smooth muscle cells (PASMCs). In a preliminary study, the 
      human PASMCs were stimulated by a variety of concentrations of CRP (5-200 
      microg/mL) at different time points (0, 3, 6, 9, 12, 18 and 24 h) for the purpose 
      of determining the dose- and time-dependent effects of CRP on inflammatory 
      response of the cells. Then, the cells were pre-incubated for 2 h with 
      atorvastatin (0.1-10 micromol/L) in the presence of CRP. The supernatant levels 
      of both IL-6 and MCP-1 secretion were examined by ELISA. The cellular mRNA 
      expressions of IL-6 and MCP-1 and nuclear factor-kappaB (NF-kappaB) activity were 
      determined by real-time reverse transcription and polymerase chain reaction 
      (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. CRP 
      resulted in elevated IL-6 and MCP-1 secretion and mRNA expression in a dose- and 
      time-dependent manner. In addition, CRP also significantly activated the 
      NF-kappaB pathway. Preincubation with 0.1-10 micromol/L of atorvastatin 
      significantly decreased the secretions of IL-6 and MCP-1 induced by CRP. 
      Moreover, 10 micromol/L of atorvastatin completely abrogated CRP-induced increase 
      in IL-6 and MCP-1 by attenuating the activation of NF-kappaB. The present study 
      demonstrated that inhibiting effect of atorvastatin on CRP-induced inflammatory 
      response in cultured PASMCs was associated with NF-kappaB pathway. This pathway 
      might represent a promising target for controlling CRP-induced inflammatory 
      response in pulmonary arterial diseases.
FAU - Li, Jie
AU  - Li J
AD  - Department of Cardiology, Cardiovascular Institute & Fu Wai Hospital, Peking 
      Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, 
      China.
FAU - Li, Jian-Jun
AU  - Li JJ
FAU - He, Jian-Guo
AU  - He JG
FAU - Nan, Jing-long
AU  - Nan JL
FAU - Guo, Yuan-lin
AU  - Guo YL
FAU - Xiong, Chang-ming
AU  - Xiong CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Ther
JT  - Cardiovascular therapeutics
JID - 101319630
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrroles)
RN  - 0 (RNA, Messenger)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
CIN - Cardiovasc Ther. 2010 Spring;28(1):1-4. PMID: 20074252
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Atorvastatin
MH  - C-Reactive Protein/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Heptanoic Acids/*pharmacology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
MH  - Inflammation Mediators/*metabolism
MH  - Interleukin-6/genetics
MH  - Muscle, Smooth, Vascular/*drug effects/immunology
MH  - Myocytes, Smooth Muscle/*drug effects/immunology
MH  - NF-kappa B/*metabolism
MH  - Pulmonary Artery/drug effects/immunology
MH  - Pyrroles/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - Time Factors
EDAT- 2010/01/16 06:00
MHDA- 2010/03/12 06:00
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/03/12 06:00 [medline]
AID - CDR103 [pii]
AID - 10.1111/j.1755-5922.2009.00103.x [doi]
PST - ppublish
SO  - Cardiovasc Ther. 2010 Spring;28(1):8-14. doi: 10.1111/j.1755-5922.2009.00103.x.