PANoptosis: A new perspective on the pathogenesis of cardiovascular diseases

PANoptosis, a newly identified programmed cell death pathway, clarifies the complex cross-talk among pyroptosis, apoptosis, and necroptosis. Its initiation involves the assembly and activation of PANoptosomes, which, despite varying in composition, converge on key molecules in pyroptosis, apoptosis, and necroptosis pathways to induce cell death. This process is regulated by various effector molecules across stages, including receptor-ligand binding, PANoptosome assembly, and downstream pathway activation. As an emerging cell death mechanism, PANoptosis is gaining increasing significance in cardiovascular diseases (CVDs). In the pathological damage resulting from atherosclerosis and myocardial ischemia-reperfusion injury, various cell types – including cardiomyocytes, cardiac fibroblasts, vascular endothelial and smooth muscle cells, and monocytes/macrophages – undergo pyroptosis, apoptosis, and necroptosis. Meanwhile, indirect or direct evidence of PANoptosis has been found in related cells of many other heart diseases and vascular diseases, all of which suggest that PANoptosis may be involved in the pathogenesis of CVDs. The mechanisms of PANoptosis in CVDs are significant and complex, but they have not yet been systematically organized and differentiated. This review consolidates the components, mechanisms, and regulatory frameworks of PANoptosis, systematically compiles the advancements in research pertaining to PANoptosis in CVDs, and illuminates the shared features and distinctions of PANoptosis across different cardiovascular conditions.