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Rupture of aortic aneurysm and dissection (AAD) remains a leading cause of death. Progressive smooth muscle cell (SMC) loss is a crucial feature of AAD that contributes to aortic dysfunction and degeneration, leading to aortic aneurysm, dissection, and, ultimately, rupture. Understanding the molecular mechanisms of SMC loss and identifying pathways that promote SMC death in AAD are critical for developing an effective pharmacologic therapy to prevent aortic destruction and disease progression. Cell death is controlled by programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. Although these pathways share common stimuli and triggers, each type of programmed cell death has unique features and activation pathways. A growing body of evidence supports a critical role for programmed cell death in the pathogenesis of AAD, and inhibitors of various types of programmed …