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The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning

Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic...

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Autores principales: Vinokur, Vladimir, Berenshtein, Eduard, Bulvik, Baruch, Grinberg, Leonid, Eliashar, Ron, Chevion, Mordechai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655153/
https://www.ncbi.nlm.nih.gov/pubmed/23690966
http://dx.doi.org/10.1371/journal.pone.0062948
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author Vinokur, Vladimir
Berenshtein, Eduard
Bulvik, Baruch
Grinberg, Leonid
Eliashar, Ron
Chevion, Mordechai
author_facet Vinokur, Vladimir
Berenshtein, Eduard
Bulvik, Baruch
Grinberg, Leonid
Eliashar, Ron
Chevion, Mordechai
author_sort Vinokur, Vladimir
collection PubMed
description Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection.
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spelling pubmed-36551532013-05-20 The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning Vinokur, Vladimir Berenshtein, Eduard Bulvik, Baruch Grinberg, Leonid Eliashar, Ron Chevion, Mordechai PLoS One Research Article Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection. Public Library of Science 2013-05-15 /pmc/articles/PMC3655153/ /pubmed/23690966 http://dx.doi.org/10.1371/journal.pone.0062948 Text en © 2013 Vinokur et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vinokur, Vladimir
Berenshtein, Eduard
Bulvik, Baruch
Grinberg, Leonid
Eliashar, Ron
Chevion, Mordechai
The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title_full The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title_fullStr The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title_full_unstemmed The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title_short The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning
title_sort bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655153/
https://www.ncbi.nlm.nih.gov/pubmed/23690966
http://dx.doi.org/10.1371/journal.pone.0062948
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