| PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts. | |
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MedLine Citation:
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PMID: 17320065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Vishnu Chintalgattu; Gregory S Harris; Shaw M Akula; Laxmansa C Katwa |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-01-17 |
Journal Detail:
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Title: Cardiovascular research Volume: 74 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-13 Completed Date: 2007-06-21 Revised Date: 2011-09-22 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 140-50 Citation Subset: IM |
Affiliation:
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Department of Physiology, The Brody School of Medicine, East Carolina University Greenville, NC 27834, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL-R01-60047/HL/NHLBI NIH HHS; R01 HL060047-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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