Immunometabolism of Phagocytes and Relationships to Cardiac Repair

Frontiers in Cardiovascular Medicine

Esther Liu¹  Laurent Yvan-Charvet²  Amanda Becker³  Connor Lantz⁴  Shuang Zhang⁴  Michael M. Abecassis⁴  Russel Emmons⁴  Edward B. Thorp⁵  Gael Bories⁵ 

[1]Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL, United States

[2]Comprehensive Transplant Center, Northwestern Feinberg School of Medicine, Chicago, IL, United States

[3]

[4]Department of Pediatrics, Ann &Departments of Pathology and Pediatrics, Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

[5]UMR INSERM U1065/UNS, C3M, Bâtiment Universitaire ARCHIMED, Nice, France

关键词: macrophage;    neutrophil;    phagocyte;    immunometabolism;    hypoxia;    reperfusion;   

DOI  :  10.3389/fcvm.2019.00042

来源: DOAJ

【 摘 要 】

Cardiovascular disease remains the leading cause of death worldwide. Myocardial ischemia is a major contributor to cardiovascular morbidity and mortality. In the case of acute myocardial infarction, subsequent cardiac repair relies upon the acute, and coordinated response to injury by innate myeloid phagocytes. This includes neutrophils, monocytes, macrophage subsets, and immature dendritic cells. Phagocytes function to remove necrotic cardiomyocytes, apoptotic inflammatory cells, and to remodel extracellular matrix. These innate immune cells also secrete cytokines and growth factors that promote tissue replacement through fibrosis and angiogenesis. Within the injured myocardium, macrophages polarize from pro-inflammatory to inflammation-resolving phenotypes. At the core of this functional plasticity is cellular metabolism, which has gained an appreciation for its integration with phagocyte function and remodeling of the transcriptional and epigenetic landscape. Immunometabolic rewiring is particularly relevant after ischemia and clinical reperfusion given the rapidly changing oxygen and metabolic milieu. Hypoxia reduces mitochondrial oxidative phosphorylation and leads to increased reliance on glycolysis, which can support biosynthesis of pro-inflammatory cytokines. Reoxygenation is permissive for shifts back to mitochondrial metabolism and fatty acid oxidation and this is ultimately linked to pro-reparative macrophage polarization. Improved understanding of mechanisms that regulate metabolic adaptations holds the potential to identify new metabolite targets and strategies to reduce cardiac damage through nutrient signaling.

【 授权许可】

Unknown