Immunometabolic cross-talk in the inflamed heart
Authors:Federica M. Marelli-Berg1,3 and Dunja Aksentijevic2,3
1 William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
2 School of Biological and Chemical Sciences, Queen Mary University of London, G.E. Fogg Building, Mile End Road, London E1 4NS, United Kingdom.
3 Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Keywords:
heart, inflammation, metabolism, innate immune response, adaptive immune responses.
Abbreviatons:
AMPK – AMP-activated protein kinase,
ATP – adenosine triphosphate,
CAD – coronary artery disease,
CK – creatine kinase,
CMR – cardiac magnetic resonance,
CRP – C-reactive protein,
DAG – diacylglycerol,
DC – dendritic cell,
DCM – dilated cardiomyopathy,
ERR – estrogen-related receptor,
ETC – electron transport chain,
FA – fatty acid,
FFA – free FA,
GC – germinal center,
HFpEF – HF with preserved ejection fraction,
HIF – hypoxia¬inducible factor,
IL – interleukin,
LDH – lactate dehydrogenase,
LV – left ventricular,
LPS – lipopolysaccharide,
MCT – monocarboxylate transporter,
MI – myocardial infarction,
MIF – migration inhibitory factor,
mTOR – mammalian target of rapamycin,
NK – natural killer,
OXPHOS – oxidative phosphorylation,
PARP – poly-(ADP-ribose)-polymerase,
PCr – phosphocreatine,
PDH – pyruvate dehydrogenase,
PFK – phosphofructokinase,
PKC – protein kinase C,
PPAR – peroxisome proliferator¬activated receptor,
ROS – reactive oxygen species,
T1D – type 1 diabetes,
T2D – type 2 diabetes,
TAG – triacylglycerol,
TCR – T cell receptor,
TNF – tumor necrosis factor,
Treg – regulatory T cell,
TTA – tetradecythioacetic acid.
Corresponding Author(s):
Conflict of interest statement:
None.
Please cite this article as:
Federica M. Marelli-Berg and Dunja Aksentijevic (2019). Immunometabolic cross-talk in the inflamed heart. Cell Stress 3(8): 240-266. doi: 10.15698/cst2019.08.194
© 2019 Morelli-Berg and Aksentijevic. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and re-production in any medium, provided the original author and source are acknowledged.
Abstract:
Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune cells during inflammation, and we discuss potential key mechanisms by which these metabolic responses intersect and influence each other and ultimately define the prognosis of the inflammatory process in the heart.