title: Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chun
authors.forename: Wang
authors.initials: W
authors.lastname: Yang
authors.forename: Cai
authors.initials: C
authors.lastname: Xueding
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qi
authors.forename: Huang
authors.initials: H
authors.lastname: Xiaoying
authors.forename: Xu
authors.initials: X
authors.lastname: Honglei
authors.forename: Yu
authors.initials: Y
authors.lastname: Fangyou
authors.forename: Chen
authors.initials: C
authors.lastname: Chan
authors.forename: Lu
authors.initials: L
authors.lastname: Yuanyuan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Weixi
authors.forename: Yao
authors.initials: Y
authors.lastname: Dan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhoucang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lehe
authors.forename: Ding
authors.initials: D
authors.lastname: Cheng
authors.forename: Wang
authors.initials: W
authors.lastname: Liangxing
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008297:Male; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology
chemical_list: D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D011725:Pyridines; D012333:RNA, Messenger; D013267:Stilbenes; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000077185:Resveratrol