Eosinophil Deficiency Promotes Aberrant Repair and Adverse Remodeling Following Acute Myocardial Infarction

Toor, Iqbal; Rückerl, Dominik; Mair, Iris; Ainsworth, Rob; Meloni, Marco; Spiroski, Ana-Mishel; Benezech, C; Felton, Jennifer M; Thomson, Adrian; Caporali, Andrea; Keeble, Thomas R.; Tang, Kare; Rossi, Adriano G.; Newby, David E.; Allen, Judith E.; Gray, Gillian A.

doi:10.1016/j.jacbts.2020.05.005

Cited by 56 publications

(53 citation statements)

References 38 publications

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“…Eosinophils also secrete IL-4, cytokine playing an essential role in differentiation of macrophages towards M2 phenotype, and regulating myocardial tissue regeneration ( 53 , 54 ). Eosinophilic cationic protein mEar1 together with IL-4 was able to inhibit apoptosis is cardiomyocytes and prevent adhesion of neutrophils to endothelial wall, improving cardiac dysfunction ( 49 ).…”

Section: Eosinophilsmentioning

confidence: 99%

“…Eosinophilic cationic protein mEar1 together with IL-4 was able to inhibit apoptosis is cardiomyocytes and prevent adhesion of neutrophils to endothelial wall, improving cardiac dysfunction ( 49 ). Most likely production of IL-4 is a key feature providing beneficial effects of eosinophils during AMI, as injection of the recombinant IL-4 to eosinophil-deficient mice rescued adverse remodeling of the left ventricle after the permanent ligation of the left coronary artery ( 54 ). However, the potency of treatment with IL-4 appeared to be time-dependent: administration of IL-4 lost its efficiency when injected at the advanced stages of the post-MI remodeling ( 55 ).…”

Section: Eosinophilsmentioning

confidence: 99%

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Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

et al. 2021

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The burden of heart failure (HF), developing after myocardial infarction MI, still represents a major issue in clinical practice. Failure of appropriate resolution of inflammation during post-myocardial injury is associated with unsuccessful left ventricular remodeling and underlies HF pathogenesis. Cells of the immune system have been shown to mediate both protective and damaging effects in heart remodeling. This ambiguity of the role of the immune system and inconsistent results of the recent clinical trials question the benefits of anti-inflammatory therapies during acute MI. The present review will summarize knowledge of the roles that different cells of the immune system play in the process of post-infarct cardiac healing. Data on the phenotype, active molecules and functions of the immune cells, based on the results of both experimental and clinical studies, will be provided. For some cellular subsets, such as macrophages, neutrophils, dendritic cells and lymphocytes, an anti-inflammatory activity has been attributed to the specific subpopulations. Activity of other cells, such as eosinophils, mast cells, natural killer (NK) cells and NKT cells has been shown to be highly dependent of the signals created by micro-environment. Also, new approaches for classification of cellular phenotypes based on the single-cell RNA sequencing allow better understanding of the phenotype of the cells involved in resolution of inflammation. Possible perspectives of immune-mediated therapy for AMI patients are discussed in the conclusion. We also outline unresolved questions that need to be solved in order to implement the current knowledge on the role of the immune cells in post-MI tissue repair into practice.

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Section: Eosinophilsmentioning

confidence: 99%

Section: Eosinophilsmentioning

confidence: 99%

Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

et al. 2021

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“…Notably, ΔdblGATA mice had a higher number of pro-inflammatory neutrophils and macrophages. Moreover, the expression of CD206, a marker for macrophage activation was reduced in ΔdblGATA mice but restored by intra-peritoneal eosinophil replenishment 70 . This clearly demonstrates the importance of eosinophils in inflammatory resolution.…”

Section: Eosinophils Help To Establish An Anti-inflammatory Environmentmentioning

confidence: 97%

“…However, functional studies have yet to assess the impact of these cells on regeneration. Interestingly, treatment of ΔdblGATA mice with IL-4 complexes, which are typically stored within pre-formed eosinophil granules, successfully rescued the adverse cardiac remodelling observed in these mice 70 . IL-4 mediated activation of macrophages is associated with a wound-healing phenotype.…”

Section: Eosinophils Help To Establish An Anti-inflammatory Environmentmentioning

confidence: 99%

Immunomodulation for optimal cardiac regeneration: insights from comparative analyses

Trajano

Smart

2021

npj Regen Med

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Despite decades of research, regeneration of the infarcted human heart remains an unmet ambition. A significant obstacle facing experimental regenerative therapies is the hostile immune response which arises following a myocardial infarction (MI). Upon cardiac damage, sterile inflammation commences via the release of pro-inflammatory meditators, leading to the migration of neutrophils, eosinophils and monocytes, as well as the activation of local vascular cells and fibroblasts. This response is amplified by components of the adaptive immune system. Moreover, the physical trauma of the infarction and immune-mediated tissue injury provides a supply of autoantigens, perpetuating a cycle of autoreactivity, which further contributes to adverse remodelling. A gradual shift towards an immune-resolving environment follows, culminating in the formation of a collagenous scar, which compromises cardiac function, ultimately driving the development of heart failure. Comparing the human heart with those of animal models that are capable of cardiac regeneration reveals key differences in the innate and adaptive immune responses to MI. By modulating key immune components to better resemble those of regenerative species, a cardiac environment may be established which would, either independently or via the synergistic application of emerging regenerative therapies, improve functional recovery post-MI.

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“…Eosinophils are an understudied immune cell population in the ischemic heart. It was recently shown that eosinophil depletion worsened cardiac outcomes after permanent coronary artery occlusion, indicating this immune cell population warrants further investigation [26].…”

Section: Myeloid Cell Activity After Myocardial Infarctionmentioning

confidence: 99%

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

Tobin

Alibhai

Weisel

et al. 2020

Cells

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The importance of the immune system for cardiac repair following myocardial infarction is undeniable; however, the complex nature of immune cell behavior has limited the ability to develop effective therapeutics. This limitation highlights the need for a better understanding of the function of each immune cell population during the inflammatory and resolution phases of cardiac repair. The development of reliable therapies is further complicated by aging, which is associated with a decline in cell and organ function and the onset of cardiovascular and immunological diseases. Aging of the immune system has important consequences on heart function as both chronic cardiac inflammation and an impaired immune response to cardiac injury are observed in older individuals. Several studies have suggested that rejuvenating the aged immune system may be a valid therapeutic candidate to prevent or treat heart disease. Here, we review the basic patterns of immune cell behavior after myocardial infarction and discuss the autonomous and nonautonomous manners of hematopoietic stem cell and immune cell aging. Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.

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Eosinophil Deficiency Promotes Aberrant Repair and Adverse Remodeling Following Acute Myocardial Infarction

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Cited by 56 publications

References 38 publications

Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

Immunomodulation for optimal cardiac regeneration: insights from comparative analyses

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

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