Immunometabolic cross-talk in the inflamed heart

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.

Influenza-associated cardiac injury: a disease of the cardiac conduction system?

“…Interestingly, there was a lack of significant myocardial fibrosis and inflammatory infiltrates in the infected mice in contrast to reports from patients with Influenza 4 , but it should also be noted that histopathology analysis was performed only at 4 days post-infection. Accordingly, the authors report increased transcription of cytokines such as IL-1 and IL-6, suggesting activation of innate immunity, which can also indirectly affect cardiomyocyte function 7 and induce a status of metabolic stress, as reported in the study. The ability of these cytokines to alter the heart conduction system remains unexplored.…”

The immunosuppression of macrophages underlies the cardioprotective effects of catestatin (CST)

“…Therefore, mitochondrial health is critical for the proper functioning of the heart. A plethora of substrate are used to produce ATP, including FA, glucose, lactate, and ketones (33,59) and substrate selection depends largely on substrate availability, oxygen concentration and myocardial workload (60). Under normal conditions, the heart relies predominantly (~60-90%) on FA oxidation to fuel ATP production, whereas the remaining ~10-40% of ATP is derived from pyruvate oxidation (61).…”

Senescence and Type 2 Diabetic Cardiomyopathy: How Young Can You Die of Old Age?

“…Thus, the use of the term "diabetic cardiomyopathy" has been extended to describe the increased susceptibility of the T2D heart to dysfunction. The mechanisms by which T2D leads to dbCM have been extensively reviewed elsewhere (Kenny and Abel, 2019;Marelli-Berg and Aksentijevic, 2019;Tan et al, 2020). However, the principal pathways that…”

“…Substrate usage by the heart is flexible, as the substrate utilisation ratio is rapidly adjusted in order to maintain a continuous ATP supply (reviewed in (Lopaschuk et al, 2021)). Severe metabolic alterations characterise the diabetic heart, with changes in substrate utilization, alterations in mitochondrial organisation and function, together with enhanced ROS production all being observed and which collectively lead to energetic deficit (reviewed in (Marelli-Berg and Aksentijevic, 2019)).…”

“…Mechanisms are mainly directed towards the activation of the NF-κB pathway. This mechanism is prevalent in diabetic vasculature and myocardium contributing to damage by upregulation of cytokines (TGF-β1, IL-1β, IL-6, IL-18, TNF-α), chemokines and adhesion molecules (Baker et al, 2011;Gordon et al, 2011;Shah and Brownlee, 2016;Marelli-Berg and Aksentijevic, 2019). Furthermore, cardiomyocyte-specific overexpression of IκB-α protein, suppressor of the canonical NF-κB signalling pathway, prevented streptozotocin-induced diabetic cardiomyopathy by inhibiting the renin-angiotensin system (Thomas et al, 2014).…”