2026-04-13T07:59:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4552162026-03-13T07:01:55Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Zuurbier, Coert J. author Bertrand, Luc author Beauloye, Christoph R. author Andreadou, Ioanna author Ruiz Meana, Marisol author Jespersen, Nichlas R. author Kula-Alwar, Duvaraka author Prag, Hiran A. author Eric Botker, Hans author Dambrova, Maija author Montessuit, Christophe author Kaambre, Tuuli author Liepinsh, Edgars author Brookes, Paul S. author Krieg, Thomas author Universitat Autònoma de Barcelona author 2020 Reducing infarct size during a cardiac ischaemic-reperfusion episode is still of paramount importance, because the extension of myocardial necrosis is an important risk factor for developing heart failure. Cardiac ischaemia-reperfusion injury (IRI) is in principle a metabolic pathology as it is caused by abruptly halted metabolism during the ischaemic episode and exacerbated by sudden restart of specific metabolic pathways at reperfusion. It should therefore not come as a surprise that therapy directed at metabolic pathways can modulate IRI. Here, we summarize the current knowledge of important metabolic pathways as therapeutic targets to combat cardiac IRI. Activating metabolic pathways such as glycolysis (eg AMPK activators), glucose oxidation (activating pyruvate dehydrogenase complex), ketone oxidation (increasing ketone plasma levels), hexosamine biosynthesis pathway (O-GlcNAcylation; administration of glucosamine/glutamine) and deacetylation (activating sirtuins 1 or 3; administration of NAD + -boosting compounds) all seem to hold promise to reduce acute IRI. In contrast, some metabolic pathways may offer protection through diminished activity. These pathways comprise the malate-aspartate shuttle (in need of novel specific reversible inhibitors), mitochondrial oxygen consumption, fatty acid oxidation (CD36 inhibitors, malonyl-CoA decarboxylase inhibitors) and mitochondrial succinate metabolism (malonate). Additionally, protecting the cristae structure of the mitochondria during IR, by maintaining the association of hexokinase II or creatine kinase with mitochondria, or inhibiting destabilization of FF-ATPase dimers, prevents mitochondrial damage and thereby reduces cardiac IRI. Currently, the most promising and druggable metabolic therapy against cardiac IRI seems to be the singular or combined targeting of glycolysis, O-GlcNAcylation and metabolism of ketones, fatty acids and succinate. Ischemia Metabolism Mitochondria Cardiac metabolism as a driver and therapeutic target of myocardial infarction