Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia‐Induced Atrial Fibrillation

Uemura, Kenshi; Kondo, Hidekazu; Ishii, Yumi; Kobukata, Mami; Haraguchi, Miho; Imamura, Takaaki; Otsubo, Toyokazu; Ikebe-Ebata, Yuki; Abe, Ichitaro; Ayabe, Reika; Saito, Shotaro; Aoki, Koji; Nagano-Torigoe, Yasuko; Akioka, Hidefumi; Shinohara, Tetsuji; Teshima, Yasushi; Masaki, Takayuki; Yufu, Kunio; Nakagawa, Mikiko; Takahashi, Naohiko

doi:10.1111/jce.12995

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…Mast cells are present in atherosclerotic lesions [50,93] and promote atherogenesis [89]. These cells and their mediators are also involved in cardiometabolic diseases [78], myocardial infarction [76] and remodeling [94], atrial fibrillation [95], thromboembolism [45,51,96], and myocarditis [74,97,98]. Therefore, understanding how cardiac mast cells participate in these inflammatory disorders could help in the development of targeted therapies for these common diseases.…”

Section: Discussionmentioning

confidence: 99%

Superantigenic Activation of Human Cardiac Mast Cells

Varricchi

Loffredo

Borriello

et al. 2019

IJMS

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B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.

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Section: Discussionmentioning

confidence: 99%

Superantigenic Activation of Human Cardiac Mast Cells

Varricchi

Loffredo

Borriello

et al. 2019

IJMS

View full text Add to dashboard Cite

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“…Additionally, MCs participate in lipid retention, vascular cell remodeling, and atherosclerotic plaque progression by releasing vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines, chemokines, platelet-activating factors, and proteolytic enzymes [57]. Studies also depicted the contribution of MCs to the pathogenesis of hyperglycemia-induced atrial fibrillation via the enhancement of inflammation and fibrosis with MC-deficient W/W (v) mice [58]. Cardiac MCs were supposed to be activated by metabolic byproducts resulted from hyperglycermia and then participate in the remodeling process of cardiomyopathy by releasing a multitude of cytokines and bioactive enzymes.…”

Section: Type 2 Diabetes Mellitusmentioning

confidence: 99%

Mast Cells in Diabetes and Diabetic Wound Healing

et al. 2020

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Mast cells (MCs) are granulated, immune cells of the myeloid lineage that are present in connective tissues. Apart from their classical role in allergies, MCs also mediate various inflammatory responses due to the nature of their secretory products. They are involved in important physiological and pathophysiological responses related to inflammation, chronic wounds, and autoimmune diseases. There are also indications that MCs are associated with diabetes and its complications. MCs and MC-derived mediators participate in all wound healing stages and are involved in the pathogenesis of non-healing, chronic diabetic foot ulcers (DFUs). More specifically, recent work has shown increased degranulation of skin MCs in human diabetes and diabetic mice, which is associated with impaired wound healing. Furthermore, MC stabilization, either systemic or local at the skin level, improves wound healing in diabetic mice. Understanding the precise role of MCs in wound progression and healing processes can be of critical importance as it can lead to the development of new targeted therapies for diabetic foot ulceration, one of the most devastating complications of diabetes.

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“…In a mouse model of diabetes, hyperglycemia led to mast cell infiltration in the atria, atrial fibrosis and increased AF susceptibility. Transgenic mast-cell deficiency reversed these pathological changes (Uemura et al, 2016). In a pressure-overload mouse model, activated mast cells promoted fibroblast activation and fibrosis by releasing platelet-derived growth factor α (PDGFα).…”

Section: Immune Remodeling and Structural Remodelingmentioning

confidence: 99%

Immune remodeling and atrial fibrillation

et al. 2022

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Atrial fibrillation (AF) is a highly prevalent arrhythmia that causes high morbidity and mortality. However, the underlying mechanism of AF has not been fully elucidated. Recent research has suggested that, during AF, the immune system changes considerably and interacts with the environment and cells involved in the initiation and maintenance of AF. This may provide a new direction for research and therapeutic strategies for AF. In this review, we elaborate the concept of immune remodeling based on available data in AF. Then, we highlight the complex relationships between immune remodeling and atrial electrical, structural and neural remodeling while also pointing out some research gaps in these field. Finally, we discuss several potential immunomodulatory treatments for AF. Although the heterogeneity of existing evidence makes it ambiguous to extrapolate immunomodulatory treatments for AF into the clinical practice, immune remodeling is still an evolving concept in AF pathophysiology and further studies within this field are likely to provide effective therapies for AF.

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Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia‐Induced Atrial Fibrillation

Abstract: Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.

Cited by 16 publications

References 32 publications

Superantigenic Activation of Human Cardiac Mast Cells

Superantigenic Activation of Human Cardiac Mast Cells

Mast Cells in Diabetes and Diabetic Wound Healing

Immune remodeling and atrial fibrillation

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