Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

• Published in: Redox biology Vol. 67; p. 102894
• Main Authors: Heusch, Gerd, Andreadou, Ioanna, Bell, Robert, Bertero, Edoardo, Botker, Hans-Erik, Davidson, Sean M., Downey, James, Eaton, Philip, Ferdinandy, Peter, Gersh, Bernard J., Giacca, Mauro, Hausenloy, Derek J., Ibanez, Borja, Krieg, Thomas, Maack, Christoph, Schulz, Rainer, Sellke, Frank, Shah, Ajay M., Thiele, Holger, Yellon, Derek M., Di Lisa, Fabio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2023; Elsevier
• Subjects: Cardioprotection; Humans; Infarct size; Ischemic conditioning; Mitochondrion; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial ischemia; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Oxidation-Reduction; Reactive Oxygen Species - metabolism; Reperfusion; Review; Mitochondrion; Myocardial infarction; Cardioprotection; Reperfusion; Ischemic conditioning; Infarct size; Myocardial ischemia
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2023.102894

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal. [Display omitted] •Ischemic heart disease is the most frequent cause of death worldwide.•Ischemia/reperfusion is the substrate of ischemic heart disease.•Cardioprotection reduces infarct size and coronary microvascular obstruction.•ROS are signals of cardioprotection and executors of injury.•Translation of cardioprotection to clinical benefits has been difficult so far.•The role of ROS in cardioprotection remains ambivalent.