title: Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes.
abstract: Hypertension and DM (diabetes mellitus) are common chronic disorders that often co-exist. DM and PPAR (peroxisome-proliferator-activated receptor)-γ agonists may directly impair heart function. However, the effects of DM and PPAR-γ agonists on hypertensive myocardium are not known. Hence the aim of the present study was to investigate whether DM and a PPAR-γ agonist [RGZ (rosiglitazone)] modulated the effects of hypertension on myocardial expression of PPAR isoforms. Cardiac PPAR isoforms, TNF (tumour necrosis factor)-α and IL (interleukin)-6 were evaluated by real-time PCR and Western blotting in SHRs (spontaneously hypertensive rats), diabetic SHRs, diabetic SHRs treated with RGZ (5 mg/kg of body weight) and control WKY (Wistar-Kyoto) rats. Cardiac NADPH oxidase activity was quantified using a SOD (superoxide dismutase)-sensitive cytochrome c reduction assay. When compared with hearts from control WKY rats, hearts from SHRs had decreased PPAR-α and PPAR-δ mRNA and protein levels (39 and 44% respectively for PPAR-α, and 37 and 42% respectively for PPAR-δ), but had increased PPAR-γ mRNA and protein levels (1.9- and 1.4-fold respectively). The hypertension-induced changes in mRNA and protein of cardiac PPAR isoforms were enhanced in diabetic SHRs, which were attenuated in diabetic SHRs treated with RGZ. Cardiac TNF-α and IL-6 protein levels and NADPH oxidase activities were increased in SHRs and were increased further in diabetic SHRs. RGZ treatment decreased TNF-α and IL-6 protein levels and NADPH oxidase activities in hearts from diabetic SHRs. In conclusion, these findings suggest that DM and the PPAR-γ agonist modulated the hypertensive effects on cardiac PPAR isoform expression.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, and Wan Fang Hospital, Taiwan.
authors.forename: Ting-I
authors.initials: TI
authors.lastname: Lee
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Nan-Hung
authors.initials: NH
authors.lastname: Pan
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D019255:NADPH Oxidases