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Discovery of new therapeutic redox targets for cardioprotection against ischemia/reperfusion injury and heart failure

Daiber, A; Andreadou, I; Oelze, M; Davidson, SM; Hausenloy, DJ; (2021) Discovery of new therapeutic redox targets for cardioprotection against ischemia/reperfusion injury and heart failure. Free Radical Biology and Medicine , 163 pp. 325-343. 10.1016/j.freeradbiomed.2020.12.026. Green open access

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Abstract

Global epidemiological studies reported a shift from maternal/infectious communicable diseases to chronic non-communicable diseases and a major part is attributable to atherosclerosis and metabolic disorders. Accordingly, ischemic heart disease was identified as a leading risk factor for global mortality and morbidity with a prevalence of 128 million people. Almost 9 million premature deaths can be attributed to ischemic heart disease and subsequent acute myocardial infarction and heart failure, also representing a substantial socioeconomic burden. As evidenced by typical oxidative stress markers such as lipid peroxidation products or oxidized DNA/RNA bases, the formation of reactive oxygen species by various sources (NADPH oxidases, xanthine oxidase and mitochondrial resperatory chain) plays a central role for the severity of ischemia/reperfusion damage. The underlying mechanisms comprise direct oxidative damage but also adverse redox-regulation of kinase and calcium signaling, inflammation and cardiac remodeling among others. These processes and the role of reactive oxygen species are discussed in the present review. We also present and discuss potential targets for redox-based therapies that are either already established in the clinics (e.g. guanylyl cyclase activators and stimulators) or at least successfully tested in preclinical models of myocardial infarction and heart failure (mitochondria-targeted antioxidants). However, reactive oxygen species have not only detrimental effects but are also involved in essential cellular signaling and may even act protective as seen by ischemic pre- and post-conditioning or eustress – which makes redox therapy quite challenging.

Type: Article
Title: Discovery of new therapeutic redox targets for cardioprotection against ischemia/reperfusion injury and heart failure
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.freeradbiomed.2020.12.026
Publisher version: https://doi.org/10.1016/j.freeradbiomed.2020.12.02...
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Ischemia/reperfusion injury, Heart failure, Endothelial dysfunction, Mitochondrial dysfunction, Oxidative stress, Redox drugs
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10123453
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