Multifaceted roles of neutrophils in cardiac disease

Neutrophils, the most abundant leukocytes in human blood, have long been recognized as critical first responders in the innate immune system's defense against pathogens. Some of the more notable innate antimicrobial properties of neutrophils include generation of superoxide free radicals like myeloperoxidase, production of proteases that reshape the extracellular matrix allowing for easier access to infected tissues, and release of neutrophil extracellular traps, extruded pieces of DNA that ensnare bacterial and fungi. These mechanisms developed to provide neutrophils with a vast array of specialized functions to provide the host defense against infection in an acute setting. However, emerging evidence over the past few decades has revealed a far more complex and nuanced role for these neutrophil-driven processes in various chronic conditions, particularly in cardiovascular diseases. The pathophysiology of cardiac diseases involves a complex interplay of hemodynamic, neurohumoral, and inflammatory factors. Neutrophils, as key mediators of inflammation, contribute significantly to this intricate network. Their involvement extends far beyond their classical role in pathogen clearance, encompassing diverse functions that can both exacerbate tissue damage and contribute to repair processes. Here, we consider the contributions of neutrophils to myocardial infarction, heart failure, cardiac arrhythmias, and nonischemic cardiomyopathies. Understanding these complex interactions is crucial for developing novel therapeutic strategies aimed at modulating neutrophil functions in these highly morbid cardiac diseases.