Pharmacological inhibition of GLUT1 as a new immunotherapeutic approach after myocardial infarction.

Myocardial infarction (MI) is one of the major contributors to cardiovascular morbidity and mortality. Excess inflammation significantly contributes to cardiac remodeling and heart failure after MI. Accumulating evidence has shown the central role of cellular metabolism in regulating the differentiation and function of cells. Metabolic rewiring is particularly relevant for proinflammatory responses induced by ischemia. Hypoxia reduces mitochondrial oxidative phosphorylation (OXPHOS) and induces increased reliance on glycolysis. Moreover, activation of a proinflammatory transcriptional program is associated with preferential glucose metabolism in leukocytes. An improved understanding of the mechanisms that regulate metabolic adaptations holds the potential to identify new metabolic targets and strategies to reduce ischemic cardiac damage, attenuate excess local inflammation and ultimately prevent the development of heart failure. Among possible drug targets, glucose transporter 1 (GLUT1) gained considerable interest considering its pivotal role in regulating glucose availability in activated leukocytes and the availability of small molecules that selectively inhibit it. Therefore, we summarize current evidence on the role of GLUT1 in leukocytes (focusing on macrophages and T cells) and non-leukocytes, including cardiomyocytes, endothelial cells and fibroblasts regarding ischemic heart disease. Beyond myocardial infarction, we can foresee the role of GLUT1 blockers as a possible pharmacological approach to limit pathogenic inflammation in other conditions driven by excess sterile inflammation.