Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress
Authors: Michal Laniado-Schwartzman
Nader G Abraham
Yossi Issan
Edith Hochhauser
Dan Aravot
Ran Kornowski
Komal Sodhi
Asher Shainberg
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Oxidative stress; Heme oxygenase-1 (HO-1); Diabetes; Cardiovascular disease; Myocardial infarction (MI)
Affiliations: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel-Aviv University, Petah-Tikva, Israel., Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel-Aviv University, Petah-Tikva, Israel; Cardiology Department, Rabin Medical Center, Tel-Aviv University, Petah-Tikva, Israel., Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel-Aviv University, Petah-Tikva, Israel; Cardiac Surgery department, Rabin Medical Center, Tel-Aviv University, Petah-Tikva, Israel., Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel., Department of Pharmacology, New York Medical College, Valhalla, New York, United States of America., Department of Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, United States of America.

Abstract:  Background: Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods: In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results: HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p&lt;0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p&lt;0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P&lt;0.01, P&lt;0.001, P&lt;0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p&lt;0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p&lt;0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p&lt;0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions: HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with a concomitant inhibition of pGSK3β leading to preserved mitochondrial membrane potential. 

Retracted: No

PubPeer comments:
 Figure 7 Western blot - The Bax lanes 1, 2 and 3 appear to be the same, though 3 has had the brightness altered. Lanes 4 and 5 appear to be the same, though 5 has had the aspect ratio altered. ![file] , 
 #1 I agree with these concerns. Could the authors please provide the original uncropped scans? ,