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Heme oxygenase-1: an emerging therapeutic target to curb cardiac pathology

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Abstract

Activation of heme oxygenase-1 (HO-1), a heme-degrading enzyme responsive to a wide range of cellular stress, is traditionally considered to convey adaptive responses to oxidative stress, inflammation and vasoconstriction. These diversified effects are achieved through the degradation of heme to carbon monoxide (CO), biliverdin (which is rapidly converted to bilirubin by biliverdin reductase) and ferric iron. Recent findings have added antiproliferative and angiogenic effects to the list of HO-1/CO actions. HO-1 along with its reaction products bilirubin and CO are protective against ischemia-induced injury (myocardial infarction, ischemia—reperfusion (IR)-injury and post-infarct structural remodelling). Moreover, HO-1, and CO in particular, possess acute antihypertensive effects. As opposed to these curative potentials, the long-believed protective effect of HO-1 in cardiac remodelling in response to pressure overload and type 2 diabetes mellitus (DM) has been questioned by recent work. These challenges, coupled with emerging regulatory mechanisms, motivate further in-depth studies to help understand untapped layers of HO-1 regulation and action. The outcomes of these efforts may shed new light on critical mechanisms that could be used to harness the protective potential of this enzyme for the therapeutic benefit of patients suffering from such highly prevalent cardiovascular disorders.

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Acknowledgments

In the late preparation of the paper our co-author Prof. Guro Valen passed away. GC is supported by DHU A-TVB, APHP, France. GV was a recipient of grants from the National Association for Public Health and the University of Oslo. RM is supported by a Blanc II International Grant from the Agence Nationale de la Recherche (MITO-CO), the Fonds National de la Recherche Luxembourg, a Multidisciplinary Grant from UPEC and the AREMCAR Foundation.

Conflict of interest

On behalf of all authors, the corresponding authors state that there is no conflict of interest.

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Authors and Affiliations

  1. INSERM U955, Equipe 8, Faculty of Medicine, DHU A-TVB, Hôpital Henri Mondor, APHP, Creteil, University of Paris-Est, 3rd Floor, room 3006, Paris, France

    Gabor Czibik, Geneviéve Derumeaux & Daigo Sawaki

  2. INSERM U955, Equipe 3, Faculty of Medicine, DHU A-TVB, Hôpital Henri Mondor, APHP, Creteil, University of Paris-Est, 3rd Floor, room 3014/3060, Paris, France

    Roberto Motterlini

  3. Deptartment Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Guro Valen

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  1. Gabor Czibik
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Czibik, G., Derumeaux, G., Sawaki, D. et al. Heme oxygenase-1: an emerging therapeutic target to curb cardiac pathology. Basic Res Cardiol 109, 450 (2014). https://doi.org/10.1007/s00395-014-0450-9

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