The loss of myocardial benefit following ischemic preconditioning is associated with dysregulation of iron homeostasis in diet-induced diabetes

Vladimir Vinokur, Sarah Weksler-Zangen, Eduard Berenshtein, Ron Eliashar, Mordechai Chevion

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4 Scopus citations

Abstract

Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the nondiabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders.

Original languageAmerican English
Article numbere0159908
JournalPLoS ONE
Volume11
Issue number7
DOIs
StatePublished - Jul 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Vinokur et al. 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 credited.

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