Abstract | BACKGROUND: 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 PPARδ 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 PPARδ. 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 PPARδ 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 PPARδ inhibitor, the protective effects of telmisartan were diminished. CONCLUSION:
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Authors | Wei-Ting Chang, Juei-Tang Cheng, Zhih-Cherng Chen |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 15
Issue 1
Pg. 113
(08 12 2016)
ISSN: 1475-2840 [Electronic] England |
PMID | 27519769
(Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Benzimidazoles
- Benzoates
- PPAR gamma
- STAT3 Transcription Factor
- Stat3 protein, rat
- Streptozocin
- Telmisartan
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(adverse effects, therapeutic use)
- Animals
- Benzimidazoles
(adverse effects, therapeutic use)
- Benzoates
(adverse effects, therapeutic use)
- Cell Line
- Diabetes Mellitus, Experimental
- Diabetes Mellitus, Type 1
(drug therapy, metabolism, pathology, physiopathology)
- Diabetic Cardiomyopathies
(drug therapy, metabolism, pathology, physiopathology)
- Female
- Fibrosis
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Myocardium
(metabolism, pathology)
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- PPAR gamma
(drug effects, metabolism)
- Prospective Studies
- Rats, Sprague-Dawley
- STAT3 Transcription Factor
(metabolism)
- Signal Transduction
(drug effects)
- Streptozocin
- Telmisartan
- Time Factors
- Translational Research, Biomedical
- Treatment Outcome
- Up-Regulation
- Ventricular Function, Left
(drug effects)
- Ventricular Remodeling
(drug effects)
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