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Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications
OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to rever...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Medknow Publications & Media Pvt Ltd
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830845/ https://www.ncbi.nlm.nih.gov/pubmed/29515275 http://dx.doi.org/10.4103/ijp.IJP_710_16 |
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author | Kadakol, Almesh Malek, Vajir Goru, Santosh Kumar Pandey, Anuradha Gaikwad, Anil Bhanudas |
author_facet | Kadakol, Almesh Malek, Vajir Goru, Santosh Kumar Pandey, Anuradha Gaikwad, Anil Bhanudas |
author_sort | Kadakol, Almesh |
collection | PubMed |
description | OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I.P) in male Wistar rats. T2D rats were treated with either telmisartan (10 mg/kg/day, P.O) or esculetin (50 mg/kg/day doses, P.O) or their combination for 2 weeks. Biochemical estimations, vascular reactivity, immunohistochemistry, and western blotting experiments were performed to evaluate the effects of the treatment in T2D cardiomyopathy. RESULTS: Esculetin and telmisartan combination alleviated the pathological features of T2D cardiomyopathy including metabolic perturbations, morphometric alterations, altered vascular reactivity, increased Keap1 and fibronectin expression more effectively than their respective monotherapy. This is the first report showing that telmisartan attenuates increased level of histone PTMs such as H3K9me2, H3K9Ac, H2AK119Ub, and H2BK120Ub in heart of T2D rats. The combination regimen showed a more significant reduction in augmented histone PTMs associated with T2D cardiomyopathy than their independent treatments. CONCLUSIONS: The present study demonstrates that esculetin and telmisartan combination can be an advanced pharmacological approach to ameliorate T2D cardiomyopathy which could be partially attributed to its ability to reverse the epigenetic alterations. |
format | Online Article Text |
id | pubmed-5830845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-58308452018-03-07 Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications Kadakol, Almesh Malek, Vajir Goru, Santosh Kumar Pandey, Anuradha Gaikwad, Anil Bhanudas Indian J Pharmacol Research Article OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I.P) in male Wistar rats. T2D rats were treated with either telmisartan (10 mg/kg/day, P.O) or esculetin (50 mg/kg/day doses, P.O) or their combination for 2 weeks. Biochemical estimations, vascular reactivity, immunohistochemistry, and western blotting experiments were performed to evaluate the effects of the treatment in T2D cardiomyopathy. RESULTS: Esculetin and telmisartan combination alleviated the pathological features of T2D cardiomyopathy including metabolic perturbations, morphometric alterations, altered vascular reactivity, increased Keap1 and fibronectin expression more effectively than their respective monotherapy. This is the first report showing that telmisartan attenuates increased level of histone PTMs such as H3K9me2, H3K9Ac, H2AK119Ub, and H2BK120Ub in heart of T2D rats. The combination regimen showed a more significant reduction in augmented histone PTMs associated with T2D cardiomyopathy than their independent treatments. CONCLUSIONS: The present study demonstrates that esculetin and telmisartan combination can be an advanced pharmacological approach to ameliorate T2D cardiomyopathy which could be partially attributed to its ability to reverse the epigenetic alterations. Medknow Publications & Media Pvt Ltd 2017 /pmc/articles/PMC5830845/ /pubmed/29515275 http://dx.doi.org/10.4103/ijp.IJP_710_16 Text en Copyright: © 2018 Indian Journal of Pharmacology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Research Article Kadakol, Almesh Malek, Vajir Goru, Santosh Kumar Pandey, Anuradha Gaikwad, Anil Bhanudas Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title | Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title_full | Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title_fullStr | Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title_full_unstemmed | Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title_short | Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications |
title_sort | telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of h3, h2a, and h2b histone modifications |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830845/ https://www.ncbi.nlm.nih.gov/pubmed/29515275 http://dx.doi.org/10.4103/ijp.IJP_710_16 |
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