PMID- 25131234
OWN - NLM
STAT- MEDLINE
DCOM- 20150409
LR  - 20181202
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 127
IP  - 16
DP  - 2014
TI  - Short-term intensive atorvastatin therapy improves endothelial function partly 
      via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase 
      pathway in hyperlipidemic rabbits.
PG  - 2953-9
AB  - BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of 
      which hyperlipidemia is a major classical risk factor resulting in its 
      pathogenesis and development. The aim of this study was to determine the effects 
      of short-term intensive atorvastatin (IA) therapy on vascular endothelial 
      function and explore the possible mechanisms that may help to explain the 
      clinical benefits from short-term intensive statin therapy. METHODS: After 
      exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, 
      treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, 
      C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), 
      nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation 
      function were, respectively, measured. mRNA and protein expression of CRP, TNF-alpha, 
      IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) 
      were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. 
      RESULTS: HFD increased serum inflammatory factor levels; induced significant 
      hyperlipidemia and endothelial dysfunction, including imbalance between NO and 
      ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage 
      infiltration into adipose tissue. Five-day IA therapy could significantly 
      decrease serum inflammatory factor levels and their expression in PCAT; restore 
      the balance between NO and ET-1; and improve endothelial function and macrophage 
      infiltration without significant changes in blood lipids. However, all of the 
      above were not observed in LA therapy. In vitro experiment found that 
      lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO 
      in cultured adipocytes, which could be attenuated by short-time (6 hours) 
      treatment of high-dose (5 micromol/L) but not low-dose (0.5 micromol/L) atorvastatin. In 
      addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC, a 
      potent and direct 5-LO inhibitor) could significantly downregulate the 
      above-mentioned gene expression in LPS-treated adipocytes. CONCLUSION: Short-term 
      IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, 
      which may be partly due to attenuating inflammation of PCAT through inhibiting 
      5-LO pathway.
FAU - Wang, Xiaoqiao
AU  - Wang X
AD  - Department of Anaesthesiology, Nanfang Hospital of Southern Medical University, 
      Guangzhou, Guangdong 510515 China.
FAU - Lin, Yongqin
AU  - Lin Y
AD  - Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory 
      of Electrophysiology and Arrhythmia, Guangzhou, Guangdong 510120, China.
FAU - Luo, Niansang
AU  - Luo N
AD  - Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory 
      of Electrophysiology and Arrhythmia, Guangzhou, Guangdong 510120, China.
FAU - Chen, Zhongqing
AU  - Chen Z
AD  - Department of Anaesthesiology, Nanfang Hospital of Southern Medical University, 
      Guangzhou, Guangdong 510515 China.
FAU - Gu, Miaoning
AU  - Gu M
AD  - Department of Anaesthesiology, Nanfang Hospital of Southern Medical University, 
      Guangzhou, Guangdong 510515 China.
FAU - Wang, Jingfeng
AU  - Wang J
AD  - Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory 
      of Electrophysiology and Arrhythmia, Guangzhou, Guangdong 510120, China.
FAU - Chen, Yangxin
AU  - Chen Y
AD  - Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory 
      of Electrophysiology and Arrhythmia, Guangzhou, Guangdong 510120, China. Email: 
      tjcyx1995@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Heptanoic Acids)
RN  - 0 (Pyrroles)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
SB  - IM
MH  - Adipose Tissue/*drug effects/*immunology
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/*metabolism
MH  - Atorvastatin
MH  - Heptanoic Acids/*therapeutic use
MH  - Hyperlipidemias/*drug therapy/*immunology
MH  - Inflammation/*drug therapy/immunology
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Pyrroles/*therapeutic use
MH  - Rabbits
EDAT- 2014/08/19 06:00
MHDA- 2015/04/10 06:00
CRDT- 2014/08/19 06:00
PHST- 2014/08/19 06:00 [entrez]
PHST- 2014/08/19 06:00 [pubmed]
PHST- 2015/04/10 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2014;127(16):2953-9.