PCSK9 contributes to the development and progression of heart failure by promoting cardiomyocyte apoptosis, pyroptosis, and ferroptosis through mechanisms involving mitochondrial dysfunction, reactive oxygen species overproduction, NLRP3 inflammasome activation, and TLR4-mediated suppression of GPX4, in response to stressors such as hypoxia, ischemia/reperfusion, and oxidative stress, with observations in both animal models and human cardiac tissue, indicating direct pathological effects on the heart beyond lipid metabolism.

PCSK9 contributes to heart failure development and progression by promoting cardiomyocyte apoptosis, pyroptosis, and ferroptosis—forms of programmed cell death—through mechanisms involving mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, NLRP3 inflammasome activation, and TLR4-mediated suppression of GPX4. These processes occur in response to stressors such as hypoxia, ischemia/reperfusion, and oxidative stress, and are observed in both animal models and human cardiac tissue, suggesting PCSK9 has direct pathological effects on the heart beyond lipid metabolism.