Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron...

Full description

Bibliographic Details
Main Authors: Das, Subhash K., Wang, Wang, Zhabyeyev, Pavel, Basu, Ratnadeep, McLean, Brent, Fan, Dong, Parajuli, Nirmal, DesAulniers, Jessica, Patel, Vaibhav B., Hajjar, Roger J., Dyck, Jason R. B., Kassiri, Zamaneh, Oudit, Gavin Y.
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671148/
id pubmed-4671148
recordtype oai_dc
spelling pubmed-46711482015-12-11 Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy Das, Subhash K. Wang, Wang Zhabyeyev, Pavel Basu, Ratnadeep McLean, Brent Fan, Dong Parajuli, Nirmal DesAulniers, Jessica Patel, Vaibhav B. Hajjar, Roger J. Dyck, Jason R. B. Kassiri, Zamaneh Oudit, Gavin Y. Article Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload. Nature Publishing Group 2015-12-07 /pmc/articles/PMC4671148/ /pubmed/26638758 http://dx.doi.org/10.1038/srep18132 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Das, Subhash K.
Wang, Wang
Zhabyeyev, Pavel
Basu, Ratnadeep
McLean, Brent
Fan, Dong
Parajuli, Nirmal
DesAulniers, Jessica
Patel, Vaibhav B.
Hajjar, Roger J.
Dyck, Jason R. B.
Kassiri, Zamaneh
Oudit, Gavin Y.
spellingShingle Das, Subhash K.
Wang, Wang
Zhabyeyev, Pavel
Basu, Ratnadeep
McLean, Brent
Fan, Dong
Parajuli, Nirmal
DesAulniers, Jessica
Patel, Vaibhav B.
Hajjar, Roger J.
Dyck, Jason R. B.
Kassiri, Zamaneh
Oudit, Gavin Y.
Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
author_facet Das, Subhash K.
Wang, Wang
Zhabyeyev, Pavel
Basu, Ratnadeep
McLean, Brent
Fan, Dong
Parajuli, Nirmal
DesAulniers, Jessica
Patel, Vaibhav B.
Hajjar, Roger J.
Dyck, Jason R. B.
Kassiri, Zamaneh
Oudit, Gavin Y.
author_sort Das, Subhash K.
title Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
title_short Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
title_full Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
title_fullStr Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
title_full_unstemmed Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
title_sort iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy
description Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671148/
_version_ 1613510065008934912

Similar Items