Pauley Heart Center, Department of Internal Medicine, Cardiology, Virginia Commonwealth University, Richmond, VA.
Department of Internal Medicine, Sections on Cardiovascular Medicine, Department of Pathology, Section on Comparative Medicine, Wake Forest, School of Medicine, Winston-Salem, NC.
Transl Res. 2023 Feb;252:9-20. doi: 10.1016/j.trsl.2022.08.004. Epub 2022 Aug 7.
Despite significant advances and the continuous development of novel, effective therapies to treat a variety of malignancies, cancer therapy-induced cardiotoxicity has been identified as a prominent cause of morbidity and mortality, closely competing with secondary malignancies. This unfortunate limitation has prompted the inception of the field of cardio-oncology with its purpose to provide the necessary knowledge and key information on mechanisms that support the use of the most efficacious cancer therapy with minimal or no interruption while paying close attention to preventing cardiovascular related morbidity and mortality. Several mechanisms that contribute to cancer therapy-induced cardiotoxicity have been proposed and studied. These mainly involve mitochondrial dysfunction and reactive oxygen species-induced oxidative stress, lysosomal damage, impaired autophagy, cell senescence, DNA damage, and sterile inflammation with the formation and activation of the NLRP3 inflammasome. In this review, we focus on describing the principal mechanisms for different classes of cancer therapies that lead to cardiotoxicity involving the NLRP3 inflammasome. We also summarize current evidence of cardio-protection with inflammasome inhibitors in the context of heart disease in general, and further highlight the potential application of this evidence for clinical translation in at risk patients for the purpose of preventing cancer therapy associated cardiovascular morbidity and mortality.
尽管在治疗各种恶性肿瘤方面取得了重大进展和不断开发新型、有效的治疗方法，但癌症治疗相关的心脏毒性已成为发病率和死亡率的主要原因，与继发性恶性肿瘤密切相关。这一不幸的局限性促使了肿瘤心脏病学领域的诞生，其目的是提供关于支持使用最有效的癌症治疗方法的必要知识和关键信息，同时尽量减少或避免中断治疗，密切关注预防心血管相关发病率和死亡率。已经提出并研究了几种导致癌症治疗相关心脏毒性的机制。这些机制主要涉及线粒体功能障碍和活性氧诱导的氧化应激、溶酶体损伤、自噬受损、细胞衰老、DNA 损伤以及无病原体炎症和 NLRP3 炎性小体的形成和激活。在这篇综述中，我们重点描述了不同类型的癌症治疗方法导致心脏毒性的主要机制，这些机制涉及 NLRP3 炎性小体。我们还总结了炎性小体抑制剂在一般心脏病背景下的心脏保护作用的现有证据，并进一步强调了这一证据在有风险患者中预防癌症治疗相关心血管发病率和死亡率的潜在应用。
