Abstract

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.

Highlights

  • After myocardial infarction (MI), cardiomyocyte death activates cellular and structural remodeling of the heart: Remaining cardiomyocytes take on an additional contractile load, leading to cardiomyocyte hypertrophy, while fibroblasts proliferate, produce extracellular matrices, to help replace lost cardiomyocytes with collagenous scar

  • Anti-inflammatory medications, such as glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs) which broadly target inflammation, revealed that these drugs contribute to adverse cardiac outcomes, demonstrating the complex nature of the immune system and the recovery of cardiac function [1,2,3]

  • With aging, the heart develops an inflammaging profile, with enhanced leukocyte infiltration and cytokine production that contributes to local damage, yet aging is associated with a dampened but prolonged immune response after cardiac ischemia [164,165,166]

Read more

Summary

Introduction

After myocardial infarction (MI), cardiomyocyte death activates cellular and structural remodeling of the heart: Remaining cardiomyocytes take on an additional contractile load, leading to cardiomyocyte hypertrophy, while fibroblasts proliferate, produce extracellular matrices, to help replace lost cardiomyocytes with collagenous scar. Perhaps the most diverse and complex reaction, is the immune response which has been shown to influence multiple repair processes. There is increasing interest in developing pharmacological and cell-based therapies that target the immune response to improve cardiac repair following ischemic injury. More precise control over different populations of immune cells is required to achieve a safe and effective treatment. Another facet to the complexity of putative therapies is aging which, at the cellular level, is inherently associated with reduced cellular functionality and at the tissue level, is associated with both immunological and cardiovascular diseases. Cells 2020, 9, 1894 on the immune system and evaluates regenerative immunotherapies that may be tailored to treat cardiovascular pathologies after ischemic injury

Typical Immune Responses after Myocardial Infarction
Myeloid Cell Activity after Myocardial Infarction
Lymphoid Cell Activity after Myocardial Infarction
Dysregulation of the Immune System during Aging
Deterioration of the Bone Marrow Niche
Metabolic Adaptations
Co-Morbidities and Sex
Consequences of HSC Aging on Heart Repair and Prospective Therapies
Method
Anti-Inflammatories
Bone Marrow Transplant and Niche Remodeling
Senolytics
Findings
Conclusions and Perspectives
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call