Document Detail


PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts.
MedLine Citation:
PMID:  17320065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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.
CONCLUSION: 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:
Vishnu Chintalgattu; Gregory S Harris; Shaw M Akula; Laxmansa C Katwa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-17
Journal Detail:
Title:  Cardiovascular research     Volume:  74     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-13     Completed Date:  2007-06-21     Revised Date:  2011-09-22    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  140-50     Citation Subset:  IM    
Affiliation:
Department of Physiology, The Brody School of Medicine, East Carolina University Greenville, NC 27834, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Chromans / pharmacology*
Collagen
Drug Combinations
Enzyme-Linked Immunosorbent Assay / methods
Gene Expression Regulation
Laminin
Male
Microscopy, Fluorescence
Muscle Fibers, Skeletal / physiology
Myocardial Infarction / metabolism
Myocytes, Cardiac / metabolism*
NF-kappa B / metabolism
PPAR gamma / metabolism*
Prostaglandin D2 / analogs & derivatives*,  pharmacology
Proteoglycans
Rats
Rats, Sprague-Dawley
Receptors, Vascular Endothelial Growth Factor / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Thiazolidinediones / pharmacology*
Vascular Endothelial Growth Factor A / metabolism*
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Grant Support
ID/Acronym/Agency:
HL-R01-60047/HL/NHLBI NIH HHS; R01 HL060047-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/15-deoxyprostaglandin J2; 0/Chromans; 0/Drug Combinations; 0/Laminin; 0/NF-kappa B; 0/PPAR gamma; 0/Proteoglycans; 0/Thiazolidinediones; 0/Vascular Endothelial Growth Factor A; 119978-18-6/matrigel; 41598-07-6/Prostaglandin D2; 9007-34-5/Collagen; 97322-87-7/troglitazone; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2

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