Telmisartan improves cardiac fibrosis in diabetes through peroxisome proliferator activated receptor delta (PPAR delta): from bedside to bench

doi:10.1186/s12933-016-0430-5

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 藥學系(所) > 期刊論文 > Item 310902800/31048

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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.
關聯:	Cardiovascular Diabetology, v.15, 113
顯示於類別:	[藥學系(所)] 期刊論文

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