Glucocorticoid Receptor Antagonism and Cardiomyocyte Regeneration Following Myocardial Infarction: A Systematic Review

Myocardial regeneration has been a topic of interest in literature and research in recent years. An evolving approach reported is glucocorticoid (GC) receptor antagonism and its role in the regeneration of cardiomyocytes. The authors of this study aim to explore the reported literature on GC receptor antagonism and its effects on cardiomyocyte remodeling, hypertrophy, scar formation, and ongoing cardiomyocyte death following cardiac injury. This article overviews cellular biology, mechanisms of action, clinical implications, challenges, and future considerations. The authors of this study conducted a systematic review utilizing the Cochrane methodology and PRISMA guidelines. This study includes data collected and interpreted from 30 peer-reviewed articles from 3 databases with the topic of interest. The mammalian heart has regenerative potential during its embryonic and fetal phases which is lost during its developmental processes. The microenvironment, intrinsic molecular mechanisms, and systemic and external factors impact cardiac regeneration. GCs influence these aspects in some cases. Consequently, GC receptor antagonism is emerging as a promising potential target for stimulating endogenous cardiomyocyte proliferation, aiding in cardiomyocyte regeneration following a cardiac injury such as a myocardial infarction (MI). Experimental studies on neonatal mice and zebrafish have shown promising results with GC receptor ablation (or brief pharmacological antagonism) promoting the survival of myocardial cells, re-entry into the cell cycle, and cellular division, resulting in cardiac muscle regeneration and diminished scar formation. Transient GC receptor antagonism has the potential to stimulate cardiomyocyte regeneration and help prevent the dreaded complications of MI. More trials based on human populations are encouraged to justify their applications and weigh the risk-benefit ratio.