Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
Department of Translational Research, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
Biochem Pharmacol. 2021 Aug;190:114597. doi: 10.1016/j.bcp.2021.114597. Epub 2021 May 13.
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.
心肌梗死（MI）是心血管发病率和死亡率的主要原因之一。炎症过度会显著促进 MI 后的心脏重构和心力衰竭。越来越多的证据表明，细胞代谢在调节细胞分化和功能方面起着核心作用。代谢重编程对于缺血引起的促炎反应尤为重要。缺氧会降低线粒体氧化磷酸化（OXPHOS），并增加对糖酵解的依赖。此外，促炎转录程序的激活与白细胞中葡萄糖代谢的优先利用有关。更好地了解调节代谢适应的机制有可能确定新的代谢靶点和策略，以减少缺血性心脏损伤、减轻过度局部炎症，并最终预防心力衰竭的发生。在可能的药物靶点中，葡萄糖转运蛋白 1（GLUT1）因其在调节激活白细胞中葡萄糖可用性以及可用的选择性抑制它的小分子方面的关键作用而引起了相当大的兴趣。因此，我们总结了 GLUT1 在白细胞（重点是巨噬细胞和 T 细胞）和非白细胞中的作用的最新证据，包括心肌细胞、内皮细胞和成纤维细胞，涉及缺血性心脏病。除了心肌梗死，我们可以预见 GLUT1 阻滞剂作为一种可能的药理学方法的作用，以限制其他由过度无菌炎症驱动的致病炎症。
