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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31048


    標題: Telmisartan improves cardiac fibrosis in diabetes through peroxisome proliferator activated receptor delta (PPAR delta): from bedside to bench
    作者: Chang, Wei-Ting
    Cheng, Juei-Tang
    Chen, Zhih-Cherng
    貢獻者: Chi Mei Med Ctr, Dept Cardiol
    Chi Mei Med Ctr, Dept Med Res
    Chia Nan Univ Pharm & Sci, Dept Pharm
    關鍵字: Telmisartan
    Diabetic cardiomyopathy
    PPAR delta
    STAT3
    inflammation
    日期: 2016-08
    上傳時間: 2018-01-18 11:40:34 (UTC+8)
    出版者: Biomed Central Ltd
    摘要: Background: Despite the known risk of diabetes-induced cardiac fibrosis, less is known about whether diabetes causes an altered cardiac phenotype independent of coronary atherosclerosis. Peroxisome proliferator-activated receptor delta (PPAR delta), a versatile regulator of metabolic homeostasis, may be a potential therapeutic target. Herein we investigated the effectiveness of telmisartan, a unique angiotensin receptor blocker that increases PPAR delta expression, in improving left ventricular remodeling in diabetic humans and rats. Methods: In this longitudinal, prospective study, we enrolled 15 diabetic patients receiving telmisartan (20 mg/day) for 12 weeks. After treatment, strain was measured and compared with the baseline value. Using streptozotocin to induce type 1 diabetes rat model, we measured PPAR delta expression and downstream targets. Results: After treatment with telmisartan, both longitudinal and circumferential strains improved in diabetic patients. Compared with that of controls, the diabetic rat heart developed significant fibrosis, which markedly decreased after treatment with telmisartan (30 mg/kg/day, orally) for 7 days. After incubation with 30 mM glucose, rat cardiomyocytes showed a significant down-regulation of PPAR delta. Interestingly, the increased expression of fibrosis-associated proteins, including signal transducer and activator of transcription 3 (STAT3) was attenuated by the co-incubation of GW0742, a PPAR delta agonist. By knockdown or inhibition of STAT3, the hyperglycemia related high expression of fibrosis associated targets was reversed. Independent from the hyperglycemic incubation, STAT3 over-expression led to similar results. Conversely, in the presence of GSK0660, a PPAR delta inhibitor, the protective effects of telmisartan were diminished. Conclusion: Telmisartan improved the hyperglycemia-induced cardiac fibrosis through the PPAR delta/STAT3 pathway.
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