DeBerge Matthew, Chaudhary Rajesh, Schroth Samantha, Thorp Edward B
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
JACC Basic Transl Sci. 2023 Apr 26;8(7):884-904. doi: 10.1016/j.jacbts.2022.12.010. eCollection 2023 Jul.
Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. Although our understanding of immunometabolism has advanced rapidly over the past decade, in part through valuable insights made in cultured cells, there remains much to learn about contributions of in vivo immunometabolism and directly within the myocardium. Insight into such fundamental cell and molecular mechanisms holds potential to inform interventions that shift the balance of immunometabolism from maladaptive to cardioprotective and potentially even regenerative. Herein, we review our current working understanding of immunometabolism, specifically in the settings of sterile ischemic cardiac injury or cardiometabolic disease, both of which contribute to the onset of heart failure. We also discuss current gaps in knowledge in this context and therapeutic implications.
如今，人们越来越认识到心肌中的免疫细胞功能对心脏功能和病理生理学具有调节作用。无论是先天性免疫（包括中性粒细胞、单核细胞、树突状细胞和巨噬细胞）还是适应性免疫（包括T细胞和B细胞）都是如此。这种功能由细胞内代谢的转变驱动，如糖酵解和氧化磷酸化，以及代谢物的可用性，代谢物源自周围的细胞外环境，并在缺血和代谢综合征期间发生变化。免疫细胞与心脏实质细胞（如心肌细胞和成纤维细胞）之间的相互作用也受复杂的细胞代谢回路调节。尽管在过去十年中我们对免疫代谢的理解有了迅速进展，部分得益于在培养细胞中获得的宝贵见解，但对于体内免疫代谢以及直接在心肌中的作用仍有许多需要了解的地方。深入了解这些基本的细胞和分子机制可能为干预措施提供依据，从而将免疫代谢的平衡从适应不良转变为心脏保护甚至可能是再生性的。在此，我们综述了目前对免疫代谢的理解，特别是在无菌性缺血性心脏损伤或心脏代谢疾病的背景下，这两种情况都会导致心力衰竭的发生。我们还讨论了这方面当前的知识空白和治疗意义。
