Therapeutic implications of targeting pyroptosis in Cardiac-related etiology of heart failure.

ABSTRACT

Heart failure remains a considerable clinical and public health problem, it is the dominant cause of death from cardiovascular diseases, besides, cardiovascular diseases are one of the leading causes of death worldwide. The survival of patients with heart failure continues to be low with 45-60% reported deaths within five years. Apoptosis, necrosis, autophagy, and pyroptosis mediate cardiac cell death. Acute cell death is the hallmark pathogenesis of heart failure and other cardiac pathologies. Inhibition of pyroptosis, autophagy, apoptosis, or necrosis reduces cardiac damage and improves cardiac function in cardiovascular diseases. Pyroptosis is a form of inflammatory deliberate cell death that is characterized by the activation of inflammasomes such as NOD-like receptors (NLR), absent in melanoma 2 (AIM2), interferon-inducible protein 16 (IFI-16), and their downstream effector cytokines Interleukin IL-1ß and IL-18 leading to cell death. Recent studies have shown that pyroptosis is also the dominant cell death process in cardiomyocytes, cardiac fibroblasts, endothelial cells, and immune cells. It plays a crucial role in the pathogenesis of cardiac diseases that contribute to heart failure. This review intends to summarize the therapeutic implications targeting pyroptosis in the main cardiac pathologies preceding heart failure.