title: PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts.
abstract: OBJECTIVE
  Myofibroblasts (myoFb) are the major cell types that appear at the site of myocardial infarction (MI) in response to injury and play a vital role in tissue repair/remodeling. Since vascular endothelial growth factor (VEGF) plays a crucial role in the infarcted/ischemic heart, we hypothesized that activation of the peroxisome proliferator-activated receptor (PPAR)-gamma by its agonists induces VEGF expression while simultaneously decreasing inflammation (NF-kappaB). Such an increase in myoFb VEGF expression by PPAR-gamma agonists may play a role in angiogenesis.
  
  
  METHODS
  Rat myoFb were treated with PPAR-gamma agonists and VEGF expression was measured by ELISA. The effect of these agonists on VEGF receptors was determined by qRT-PCR and flow-cytometric analysis. VEGF produced by these cells was also used for analysis of in vitro tubule formation (Matrigel assay).
  
  
  RESULTS
  The PPAR-gamma activators troglitazone (TZ) and 15-deoxy-prostaglandin J2 (15J2) induced the expression of VEGF and its receptors (Flt-1 and KDR) in myoFb. TZ and 15J2 elicited a significant increase in the expression of KDR (14.7+/-1.0% and 9.6+/-2.1% respectively) and Flt-1 (24.5+/-2.0%, and 14.0+/-2.2% respectively) when compared to untreated myoFb. MyoFb treated with PPAR-gamma agonists increased extracellular VEGF, augmenting tubule formation on a Matrigel. The PPAR-gamma activator 15J2 significantly decreased the NF-kappaB activity in myoFb.
  
  
  CONCLUSIONS
  This study demonstrates the induction of the VEGF accompanied by a reduction of NF-kappaB activity (inflammatory signaling) by PPAR-gamma agonists in cardiac myoFb. These results may further the understanding of the beneficial effects of PPAR-gamma agonists on infarcted tissue repair and angiogenesis.
authors.affiliation: Department of Physiology, The Brody School of Medicine, East Carolina University Greenville, NC 27834, USA.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Chintalgattu
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Harris
authors.forename: Shaw M
authors.initials: SM
authors.lastname: Akula
authors.forename: Laxmansa C
authors.initials: LC
authors.lastname: Katwa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003094:Collagen; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D007797:Laminin; D008297:Male; D008856:Microscopy, Fluorescence; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011509:Proteoglycans; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; D002839:Chromans; D004338:Drug Combinations; D007797:Laminin; D016328:NF-kappa B; D047495:PPAR gamma; D011509:Proteoglycans; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077288:Troglitazone; D015230:Prostaglandin D2