Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro.

Abstract

Agonists of the peroxisome proliferator-activated receptor alpha (PPARalpha) and gamma (gamma) exert anti-proliferative and anti-inflammatory effects that led to the testing of these drugs in experimental cardiac hypertrophy. However, the effect of PPAR beta/delta (beta/delta) agonists in hypertrophy is not yet known. In this paper, an experiment was conducted to explore whether PPARbeta/delta activation has an effect on cardiac hypertrophy. An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with Angiotensin II (Ang II1micromol x L(-1)) stimulation. For the examination of PPAR beta/delta effect, the cultured rat cardiac myocytes were pretreated with GW0742 (10 micromol.L(-1)), an agonist of PPARbeta/delta, for 48h before Ang II stimulation. The following parameters in the cultured cells were determined: surface areas of myocytes were measured by the NIH Image Software; (3)H-leucine incorporation into myocytes was counted by liquid scintillometer; mRNA expression of PPARbeta/delta, ANP, BNP, MMP9, MMP2, and IL-1beta was detected by RT-PCR; PPARbeta/delta protein expression was evaluated with immunofluorescence staining; GW0742 could ameliorate Ang II-induced cardiomyocyte hypertrophy, as indicated by its inhibitory effects on the surface area of myocytes, and ANP and BNP mRNA expressions in myocytes and (3)H-leucine incorporation into myocytes. Meanwhile, GW0742 pretreatment exerted inhibition on mRNA expression augmentation of such cytokines as MMP9, MMP2, and IL-1beta in hypertrophic myocytes. In addition, the down-regulated expression of PPARbeta/delta mRNA and protein in hypertrophic myocytes was also significantly reversed by GW0742. We demonstrate for the first time that GW0742 exerts a beneficial effect on Ang II-induced cardiac hypertrophy and the relation to inflammation response.

• Authors: Li Sheng, Ping Ye, Yong-Xue Liu, Chun-Guang Han, Zhi-Yi Zhang
• Journal: Clinical and experimental hypertension (New York, N.Y. : 1993) (Clin Exp Hypertens) Vol. 30 Issue 2 Pg. 109-19 (Feb 2008) ISSN: 1525-6006 [Electronic] England
• PMID: 18293166 (Publication Type: Journal Article)

Chemical References

• Cytokines
• PPAR delta
• PPAR-beta
• RNA, Messenger
• Thiazoles
• Angiotensin II
• (4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid
• Leucine

Topics

• Angiotensin II
• Animals
• Cardiomegaly (chemically induced, metabolism, pathology, physiopathology)
• Cell Membrane (drug effects, ultrastructure)
• Cells, Cultured
• Cytokines (antagonists & inhibitors, genetics)
• Down-Regulation (drug effects)
• Fluorescent Antibody Technique
• In Vitro Techniques
• Leucine (metabolism)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• PPAR delta (agonists, genetics, metabolism)
• PPAR-beta (agonists, genetics, metabolism)
• RNA, Messenger (antagonists & inhibitors, metabolism)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Staining and Labeling
• Thiazoles (pharmacology)