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

Vladimir Vinokur, Eduard Berenshtein, Baruch Bulvik, Leonid Grinberg, Ron Eliashar, Mordechai Chevion*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageAmerican English
Article numbere62948
JournalPLoS ONE
Volume8
Issue number5
DOIs
StatePublished - 15 May 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'The Bitter Fate of the Sweet Heart: Impairment of Iron Homeostasis in Diabetic Heart Leads to Failure in Myocardial Protection by Preconditioning'. Together they form a unique fingerprint.

Cite this