Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Cardiovascular Surgery, Texas Heart Institute, 6770 Bertner Ave., Houston, TX 77030, USA.
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Cardiovascular Surgery, Texas Heart Institute, 6770 Bertner Ave., Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
J Mol Cell Cardiol. 2022 Feb;163:67-80. doi: 10.1016/j.yjmcc.2021.09.010. Epub 2021 Sep 28.
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 cell death represent a promising therapeutic strategy. This review discusses the different types of programmed cell death pathways and their features, induction, contributions to AAD development, and therapeutic potential. We also highlight the clinical significance of programmed cell death for further studies.
主动脉瘤和夹层 (AAD) 的破裂仍然是导致死亡的主要原因。平滑肌细胞 (SMC) 的进行性丧失是 AAD 的一个关键特征，它导致主动脉功能障碍和退化，导致主动脉瘤、夹层和最终破裂。了解 SMC 丧失的分子机制，并确定促进 AAD 中 SMC 死亡的途径，对于开发有效的药物治疗以防止主动脉破坏和疾病进展至关重要。细胞死亡受程序性细胞死亡途径控制，包括细胞凋亡、坏死性凋亡、细胞焦亡和铁死亡。尽管这些途径具有共同的刺激和触发因素，但每种类型的程序性细胞死亡都具有独特的特征和激活途径。越来越多的证据支持程序性细胞死亡在 AAD 发病机制中的关键作用，各种类型的程序性细胞死亡抑制剂代表了一种有前途的治疗策略。这篇综述讨论了不同类型的程序性细胞死亡途径及其特征、诱导、对 AAD 发展的贡献以及治疗潜力。我们还强调了程序性细胞死亡对进一步研究的临床意义。
