Neutrophil-mediated cardiac damage after acute myocardial infarction: Significance of defining a new target cell-type for developing cardioprotective drugs.

SIGNIFICANCE: Acute myocardial infarction (AMI) is a leading cause of death worldwide. Post-AMI survival rates have increased with the introduction of angioplasty as a primary coronary intervention. However, reperfusion after angioplasty represents a clinical paradox, restoring blood flow to the ischemic myocardium while simultaneously inducing ion and metabolic imbalances that stimulate immune cell recruitement and activation, mitochondrial dysfunction and damaging oxidant production. Recent Advances: Preclinical data indicate that these metabolic imbalances contribute to subsequent heart failure through sustaining local recruitment of inflammatory leukocytes and oxidative stress, cardiomyocyte death and coronary microvascular disturbances, which enhance adverse cardiac remodelling. Both left ventricular dysfunction and heart failure are strongly linked to inflammation and immune cell recruitment to the damaged myocardium. CRITICAL ISSUES: Therapeutic anti-inflammatory and antioxidant agents identified in preclinical trials have overall failed in clinical trials. FUTURE DIRECTIONS: The versatile neutrophil-derived heme enzyme, myeloperoxidase, is gaining attention as an important oxidative mediator of reperfusion injury, vascular dysfunction, adverse ventricular remodelling and atrial fibrillation. Accordingly, there is interest in therapeutically targeting neutrophils and myeloperoxidase activity in the setting of heart failure. Herein we discuss the role of post-AMI inflammation linked to myocardial damage and heart failure, describe previous trials targeting inflammation and oxidative stress post-AMI, highlight the potential adverse impact of neutrophil and myeloperoxidase, and detail therapeutic options available to target myeloperoxidase clinically in AMI patients.