Cardiac Repair and Immune System

Introduction:

Following a cardiac injury, the immune system helps in the repair and regeneration of the injured tissue. In this immune response, a large number of immune cells are recruited to the site of injury. It undergoes various processes and improves cardiac repair. The heart muscle cells called cardiomyocytes hardly regenerate naturally following an injury and can lead to heart failure. The immune cells play an important role in both repair by scar formation and initiation of tissue regeneration.

What Are Heart Injuries and How Does the Immune System Respond?

• The prevalence of cardiovascular diseases has increased in the past few decades and is a leading cause of mobility. The most common cardiovascular disease is myocardial infarction resulting in massive loss of cardiomyocytes and heart remodeling. This change can lead to acute heart failure and sudden cardiac arrest.

• The heart muscle cells produce innate and adaptive immune responses toward myocardial infarction. Modulating the immune components might resemble the regenerative species. An environment is created where it would independently or through the application of regenerative treatment result in the recovery from myocardial infarction.

• The available management for cardiac injury does not prevent the disease progression or restore the functioning of the heart. Ideally, these treatment procedures should provide curative options for full regeneration of the damaged heart cells.

• After a heart injury, the immune cells reach the injury site helping in scar formation. The cells release Proinflammatory cytokines and remove the dead tissue, replacing that muscle tissue with a non-contractile scar.

• Initially, the immune system produces a response that is general and non-specific. Following that, the immune system produces an adaptive immune response that is more specific to the organ and injury.

• After a cardiomyocyte death, it activates the tissue-resident immune and non-immune cells to produce Proinflammatory cytokines and chemokines. This results in the release of a large number of circulating immune cells to the heart.

• The initial immune response also identifies the inflammatory phenotypes and the number of neutrophils and macrophages in the bloodstream.

• In the final phase of the immune response, the immune cells activate the resident fibroblast and promote endothelial proliferation and promote heart repair.

• Through the process of fibrosis, muscle tissue is replaced with a noncontractile scar which is permanent.

What Is the Innate Immune Response to Heart Injury?

After a myocardial infarction, dead cardiac muscle cells release damage associated with molecular patterns (DAMPs) that act as danger signals and trigger the release of first innate immune cells.

The innate immune cells are

1. Mast Cells:

• Important initiators in the immune response.

• Produce different mediators.

• Pro-inflammatory or pro-fibrotic effects on the blood vessel wall.

• Acts on atherosclerotic plaque.

• Helps in restoring the blood flow and ensuring the availability of oxygen and nutrients.

• Release wrong inflammatory mediators like tumor necrosis factor-alpha (TNF) and mast-cell proteases.

• Signaling the neighboring macrophages, endothelial cells, and neutrophils.

• Induce migration of neutrophils to the site of injury.

2. Neutrophils:

• Recruited to the site of injury by DAMPs.

• Reach the damaged heart issue through permeable blood vessels.

• Migration of infarcted tissue and phagocytosis clearing the dead cells and debris.

• Important rolling tissue repair and generation of reactive oxygen species.

• Secretion of proteases and degrade extracellular matrix.

• Clearance of neutrophils is important to prevent further tissue damage.

• After three days post-myocardial infarction, the neutrophils reach the myocardium and disappear, and by seven days post-myocardial infarction, the neutrophils would have disappeared.

• Complete clearance of neutrophils and actively recruiting monocytes and macrophages.

3. Monocytes and Macrophages:

• Predominance immune cell type within the infarcted myocardium.

• Primary role in maintaining the circulation of different types of macrophages and dendritic cells.

• Phagocytosis of pathogens by the macrophages.

• It is the source of matrix protein degrading enzymes.

• Rupture of atherosclerotic plaque.

• Destruction of elastin integrity in the aneurysm.

• Regulation of inflammation and scar formation.

4. Eosinophils:

• Innate Immune granulocytes.

• Effector function after allergic response or infection.

• Reach the infarcted heart 24 hours post-myocardial infarction. The number of cells increases by four days post-myocardial infarction.

• Cardioprotective function by reducing cardiomyocyte death.

• Cardiac fibroblast activation

• Production of interleukin 4.

5. Innate Lymphocytes:

• Natural killer cells.

• Multiple roles in the protection of injured issues.

• Also, limit the overproduction of collagen by myofibroblasts.

• Limit apoptosis of cardiac muscle cells.

• Regulate macrophages.

• Inhibit atherosclerotic plaque formation.

What Is the Adaptive Immune Response Following a Cardiac Injury?

Following the initial immune response, the adaptive immune response takes place. The cells involved in the adaptive immune response are

1. Dendritic Cells:

• Major antigen-presenting cells

• Activate CD8 + T lymphocytes, which are antigen-specific.

• Establishes an important link between in-need and adaptive immune response.

2. T- lymphocytes:

• It Circulates CD4 T cells to the injured heart tissue and helps in myocardial wound healing.

3. B-lymphocytes:

• Production of antigen-specific immunoglobulin.

• Produce cytokines and chemokines that help in myocardial remodeling.

What Is the Significance of Immune Response in Cardiac Injury?

• In myocardial infarction, the injury causes the loss of cardiomyocytes accompanied by the formation of a fibrotic scar. This leads to a cascade of events and eventually leads to heart failure.

• The cardiomyocytes or muscle cells in mammals have limited region or capacity. Understanding the molecular pathways help in achieving cardiac regeneration.

• Various strategies, like directly programming the cardiomyocytes or manipulating the cardiac interstitium, can help repair the injured heart.

• Understanding the immune response involved in the mechanism associated with cardiac injury is important to promote tissue healing and improve the condition of the patient.

• The multi-factor immune response is to be understood properly, enabling to understanding of the reparative pathways and improving the recovery in post-myocardial infarction. Various immune-mediated cells are released, which results in reducing the symptoms and improving the condition of the heart.

Conclusion:

Myocardial infarction is a common cardiac injury. This activates an innate immune mechanism, and an improvisatory reaction is initiated. Various immune cells are recruited into the bloodstream, which helps to reduce the injury and initiate the regeneration of muscle cells. Monocytes cause phagocytosis of dead cardiomyocytes in the formation of granulation tissue and the release of growth factors. Clear knowledge about inflammatory pathways reduces cardiomyocyte injury and initiates remodeling. Other Strategies for cardiac regeneration can be studied and designed by targeting the immune response mechanism.