Banerjee Priyanka, Rosales Julia Enterría, Chau Khanh, Nguyen Minh T H, Kotla Sivareddy, Lin Steven H, Deswal Anita, Dantzer Robert, Olmsted-Davis Elizabeth A, Nguyen Hung, Wang Guangyu, Cooke John P, Abe Jun-Ichi, Le Nhat-Tu
Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, United States.
Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Cardiovasc Med. 2023 Jun 2;10:1186679. doi: 10.3389/fcvm.2023.1186679. eCollection 2023.
Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS phenotype hold promise as a therapeutic approach for managing atherosclerotic CVD in this population. This review aims to provide a mechanistic understanding of SAS induction in ECs and its contribution to atherosclerosis among cancer survivors. We delve into the mechanisms underlying EC senescence in response to disturbed flow and ionizing radiation, which play pivotal role in atherosclerosis and cancer. Key pathways, including p90RSK/TERF2IP, TGFβR1/SMAD, and BH4 signaling are explored as potential targets for cancer treatment. By comprehending the similarities and distinctions between different types of senescence and the associated pathways, we can pave the way for targeted interventions aim at enhancing the cardiovascular health of this vulnerable population. The insights gained from this review may facilitate the development of novel therapeutic strategies for managing atherosclerotic CVD in cancer survivors.
接受过治疗的癌症幸存者患动脉粥样硬化性心血管疾病(CVD)的风险增加,但其潜在机制仍不清楚。最近的研究表明,化疗可促使衰老的癌细胞获得一种称为衰老相关干性(SAS)的增殖表型。这些SAS细胞表现出更强的生长能力和对癌症治疗的抗性,从而促进疾病进展。内皮细胞(EC)衰老与动脉粥样硬化和癌症有关,包括在癌症幸存者中。癌症的治疗方式可诱导EC衰老,导致癌症幸存者出现SAS表型并随后发生动脉粥样硬化。因此,靶向具有SAS表型的衰老EC有望成为管理该人群动脉粥样硬化性CVD的一种治疗方法。本综述旨在提供对EC中SAS诱导及其对癌症幸存者动脉粥样硬化影响的机制性理解。我们深入探讨了EC对紊乱血流和电离辐射反应中衰老的潜在机制,这些在动脉粥样硬化和癌症中起关键作用。探讨了包括p90RSK/TERF2IP、TGFβR1/SMAD和BH4信号在内的关键途径作为癌症治疗的潜在靶点。通过理解不同类型衰老及其相关途径之间的异同,我们可以为旨在改善这一脆弱人群心血管健康的靶向干预措施铺平道路。本综述获得的见解可能有助于开发管理癌症幸存者动脉粥样硬化性CVD的新治疗策略。
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