Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro.
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.
Sheng
Li
L
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
Ye
Ping
P
Liu
Yong-Xue
YX
Han
Chun-Guang
CG
Zhang
Zhi-Yi
ZY
D000804:Angiotensin II; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047494:PPAR delta / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D013844:Thiazoles / Q000494:pharmacology*; D010636:Phenols; D013438:Sulfhydryl Compounds
D000804:Angiotensin II; D016207:Cytokines; D007930:Leucine; D047494:PPAR delta; D048068:PPAR-beta; D012333:RNA, Messenger; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds