PMID- 22507635
OWN - NLM
STAT- MEDLINE
DCOM- 20120626
LR  - 20181201
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 90
IP  - 19-20
DP  - 2012 May 22
TI  - Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary 
      artery hypertension via p38 mitogen-activated protein kinase and monocyte 
      chemoattractant protein-1 signaling in rats.
PG  - 721-7
LID - 10.1016/j.lfs.2012.03.008 [doi]
AB  - AIMS: In the present study, we explored the hypothesis that initiation of PH 
      involves the upregulation of monocyte chemoattractant protein-1 (MCP-1) in acute 
      PTE. We evaluated the effects of resveratrol and the role of p38 
      mitogen-activated protein kinase (MAPK) in this process. MAIN METHODS: A rat 
      model of acute PTE was established by infusion of an autologous blood clot into 
      the pulmonary artery through a polyethylene catheter. Rats were randomly divided 
      into 1, 4, and 8 hour time groups. Resveratrol, C1142 (a rodent chimeric mAb that 
      neutralizes rat MCP-1) or SB203580 (a p38MAPK specific inhibitor) was 
      administered to the animals beginning 1 h prior to the start of the acute PTE 
      protocol. At each time point, the mean pulmonary artery pressure (mPAP), mRNA and 
      protein expressions of MCP-1 were measured. The phosphorylation of p38 MAPK 
      (p-pMAPK) was also detected. KEY FINDINGS: Acute PTE elicited significant 
      increases in mean pulmonary artery pressure (mPAP), and up-regulated the 
      expression of monocyte chemoattractant protein-1 (MCP-1) and phosphorylation of 
      p38 mitogen-activated protein kinase (p-p38 MAPK). Administration of C1142 
      markedly reduced mPAP. Furthermore, pre-treatment of rats with resveratrol 
      significantly reduced mPAP and down-regulated the expression of MCP-1, which was 
      associated with robustly suppressed acute PTE-induced p-p38MAPK expression. 
      SIGNIFICANCE: These findings suggested that MCP-1 was involved in the formation 
      of acute PTE-induced PH, and resveratrol down-regulated the expression of MCP-1 
      by inhibiting acute PTE-induced p-p38MAPK activation, which contributed to the 
      decrease in PH.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Chun, Chen
AU  - Chun C
AD  - Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou 
      Medical College, Wenzhou 325000, China.
FAU - Yang, Wang
AU  - Yang W
FAU - Xueding, Cai
AU  - Xueding C
FAU - Qi, Zhang
AU  - Qi Z
FAU - Xiaoying, Huang
AU  - Xiaoying H
FAU - Honglei, Xu
AU  - Honglei X
FAU - Fangyou, Yu
AU  - Fangyou Y
FAU - Chan, Chen
AU  - Chan C
FAU - Yuanyuan, Lu
AU  - Yuanyuan L
FAU - Weixi, Zhang
AU  - Weixi Z
FAU - Dan, Yao
AU  - Dan Y
FAU - Zhoucang, Zhang
AU  - Zhoucang Z
FAU - Lehe, Yang
AU  - Lehe Y
FAU - Cheng, Ding
AU  - Cheng D
FAU - Liangxing, Wang
AU  - Liangxing W
LA  - eng
PT  - Journal Article
DEP - 20120401
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stilbenes)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Chemokine CCL2/*antagonists & inhibitors/biosynthesis/physiology
MH  - Down-Regulation/drug effects
MH  - Enzyme Inhibitors/*pharmacology/therapeutic use
MH  - Fluorescent Antibody Technique
MH  - Hypertension, Pulmonary/complications/*drug therapy
MH  - Imidazoles/pharmacology
MH  - Immunohistochemistry
MH  - Indicators and Reagents
MH  - Male
MH  - Pulmonary Embolism/complications/*drug therapy
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Resveratrol
MH  - Signal Transduction/*drug effects
MH  - Stilbenes/*pharmacology/therapeutic use
MH  - p38 Mitogen-Activated Protein Kinases/*antagonists & 
      inhibitors/biosynthesis/physiology
EDAT- 2012/04/18 06:00
MHDA- 2012/06/27 06:00
CRDT- 2012/04/18 06:00
PHST- 2011/10/01 00:00 [received]
PHST- 2012/01/27 00:00 [revised]
PHST- 2012/02/28 00:00 [accepted]
PHST- 2012/04/18 06:00 [entrez]
PHST- 2012/04/18 06:00 [pubmed]
PHST- 2012/06/27 06:00 [medline]
AID - S0024-3205(12)00131-2 [pii]
AID - 10.1016/j.lfs.2012.03.008 [doi]
PST - ppublish
SO  - Life Sci. 2012 May 22;90(19-20):721-7. doi: 10.1016/j.lfs.2012.03.008. Epub 2012 
      Apr 1.