Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases

Mangione, MariaSanta C.; Wen, Jinhua; Cao, Dian J.

doi:10.1016/j.yjmcc.2023.10.011

Cited by 4 publications

(2 citation statements)

References 176 publications

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“…During training, activation of mTOR signaling promotes glycolysis, lipid biosynthesis, and protein synthesis, supporting the metabolic demands of activated immune cells. Thus, modulation of mTOR activity/signaling can influence trained immune cell metabolism and functions ( 119 ).…”

Section: Main Textmentioning

confidence: 99%

The causes and consequences of trained immunity in myeloid cells

Bhargavi,

Subbian

2024

Front. Immunol.

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Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only the latter type has an immunological memory/recall response against specific antigens or pathogens. Recently, a new concept of trained immunity (a.k.a. innate memory response) has emerged. According to this concept, innate immune cells can exhibit enhanced responsiveness to subsequent challenges, after initial stimulation with antigen/pathogen. Thus, trained immunity enables the innate immune cells to respond robustly and non-specifically through exposure or re-exposure to antigens/infections or vaccines, providing enhanced resistance to unrelated pathogens or reduced infection severity. For example, individuals vaccinated with BCG to protect against tuberculosis were also protected from malaria and SARS-CoV-2 infections. Epigenetic modifications such as histone acetylation and metabolic reprogramming (e.g. shift towards glycolysis) and their inter-linked regulations are the key factors underpinning the immune activation of trained cells. The integrated metabolic and epigenetic rewiring generates sufficient metabolic intermediates, which is crucial to meet the energy demand required to produce proinflammatory and antimicrobial responses by the trained cells. These factors also determine the efficacy and durability of trained immunity. Importantly, the signaling pathways and regulatory molecules of trained immunity can be harnessed as potential targets for developing novel intervention strategies, such as better vaccines and immunotherapies against infectious (e.g., sepsis) and non-infectious (e.g., cancer) diseases. However, aberrant inflammation caused by inappropriate onset of trained immunity can lead to severe autoimmune pathological consequences, (e.g., systemic sclerosis and granulomatosis). In this review, we provide an overview of conventional innate and adaptive immunity and summarize various mechanistic factors associated with the onset and regulation of trained immunity, focusing on immunologic, metabolic, and epigenetic changes in myeloid cells. This review underscores the transformative potential of trained immunity in immunology, paving the way for developing novel therapeutic strategies for various infectious and non-infectious diseases that leverage innate immune memory.

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Section: Main Textmentioning

confidence: 99%

The causes and consequences of trained immunity in myeloid cells

Bhargavi,

Subbian

2024

Front. Immunol.

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“…Although not all agents are specifically designed to target monocytes or macrophages, they might still affect macrophage function. Targeting mTOR signalling in macrophages has been demonstrated to be a potential therapeutic intervention in cardiovascular diseases [ 171 ]. AMP-activated protein kinase activation in macrophages suppresses the inflammatory response [ 172 ].…”

Section: Introductionmentioning

confidence: 99%

Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension

Zuo,

Li,

Gao

et al. 2024

Respir Res

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Inflammation and immune processes underlie pulmonary hypertension progression. Two main different activated phenotypes of macrophages, classically activated M1 macrophages and alternatively activated M2 macrophages, are both involved in inflammatory processes related to pulmonary hypertension. Recent advances suggest that macrophages coordinate interactions among different proinflammatory and anti-inflammatory mediators, and other cellular components such as smooth muscle cells and fibroblasts. In this review, we summarize the current literature on the role of macrophages in the pathogenesis of pulmonary hypertension, including the origin of pulmonary macrophages and their response to triggers of pulmonary hypertension. We then discuss the interactions among macrophages, cytokines, and vascular adventitial fibroblasts in pulmonary hypertension, as well as the potential therapeutic benefits of macrophages in this disease. Identifying the critical role of macrophages in pulmonary hypertension will contribute to a comprehensive understanding of this pathophysiological abnormality, and may provide new perspectives for pulmonary hypertension management.

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Trained immunity: A link between risk factors and cardiovascular disease

Chen,

Kang,

Zhang

et al. 2024

British J Pharmacology

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Cardiovascular diseases are significant contributors to human mortality, closely associated with inflammation. With the changing living conditions and the extension of human lifespan, greater attention has been directed towards understanding the impact of early, long‐term events on the development of cardiovascular events. Lifestyle factors such as stress, unhealthy diet and physical inactivity can increase the risk of cardiovascular diseases. Interestingly, even if the risk factors are addressed later, their influence may persist. Recently, the concept of trained innate immunity (TRIM), defined as sustained alterations in the function of innate immunocyte that promote a more robust response to downstream stimuli, has been proposed to be involved in cardiovascular diseases. It is hypothesized that TRIM may serve as a mediator bridging the impacts of aforementioned risk factors. This review aims to elucidate the role of TRIM in cardiovascular diseases and highlight its significance in uncovering new mechanisms and therapeutic targets.

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Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases

Cited by 4 publications

References 176 publications

The causes and consequences of trained immunity in myeloid cells

The causes and consequences of trained immunity in myeloid cells

Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension

Trained immunity: A link between risk factors and cardiovascular disease

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