title: Fenofibrate, a peroxisome proliferator-activated receptor alpha activator, suppresses experimental autoimmune myocarditis by stimulating the interleukin-10 pathway in rats.
abstract: Experimental autoimmune myocarditis (EAM) in rats is an animal model of human giant cell myocarditis and postmyocarditis dilated cardiomyopathy. As the heart consumes large amounts of energy, heart diseases such as myocarditis and dilated cardiomyopathy are associated with abnormal fatty acid metabolism. Peroxisome proliferator-activated receptor alpha (PPARalpha) is a regulator of the oxidative degradation of fatty acids. To investigate the role of PPARalpha in EAM, fenofibrate (a PPARalpha activator) was administered to rats with EAM for 4 weeks. Reductions in the ratios of both ventricular weight to body weight and the area of inflammatory lesions to the total area of heart sections were observed in fenofibrate-treated rats when compared with controls. Fenofibrate ameliorated changes in serum albumin and sialic acid, which are markers of inflammation. Cardiac expression of interleukin-10 (IL-10) mRNA was more pronounced in the fenofibrate group than in the control group (1.3 +/- 0.2 vs 0.7 +/- 0.1; p < 0.01), and the area of intact myocardium correlated with the IL-10 mRNA level (p = 0.0297, r = 0.620). We suggest that PPARalpha activators may prevent the progression of myocarditis through increased expression of the gene encoding the anti-inflammatory cytokine IL-10, although the mechanisms involved remain to be determined.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan. maruyama@med.niigata-u.ac.jp
authors.forename: Seitaro
authors.initials: S
authors.lastname: Maruyama
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirono
authors.forename: Koichi
authors.initials: K
authors.lastname: Fuse
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011345:Fenofibrate