Natural killer cells in the heart: determinants of their protective-to-pathogenic transition and therapeutic implications

Natural killer (NK) cells are a critical component of the innate immune system and are known for their dual roles in cytotoxicity and immune regulation. While NK cells are extensively studied in infections, transplants, and cancer, their role in cardiovascular pathophysiology remains incompletely defined. Emerging evidence suggests that NK cell dysfunction not only disrupts cardiac homeostasis and contributes to cardiac inflammation, tissue remodeling, and various cardiovascular diseases. This review explores the underlying NK cell biology and function to underscore the contributions of NK cells to the cardiac microenvironment while highlighting their pathological roles and protective potential. Furthermore, we discuss the therapeutic potential of targeting NK cells in heart diseases, including recent advances in immunotherapy and various future strategies to modulate their activity for improved cardiac outcomes. Understanding the complex interplay between NK cells and the various cell types in the heart may unlock novel therapeutic avenues in cardiology.