Cancer therapy-related cardiovascular aging: mechanisms, monitoring, and intervention strategies

Figures

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  Figure 1. The relationship between Cancer Therapy-Related Cardiovascular Toxicity (CTR-CVT) and Cancer Therapy-Related Cardiovascular Aging (CTR-CVA). CTR-CVT is a collection of a series of acute and chronic injuries after cancer treatment. CTR-CVA essentially represents the long-term progression of acute/subacute injuries and the chronic phenotype of latent injuries in CTR-CVT. CTR-CVA is characterized by the accumulation of senescent cells, manifested as structural degeneration and functional decline of the cardiovascular system. CTR-CVT, Cancer Therapy-Related Cardiovascular Toxicity; CTR-CVA, Cancer Therapy-Related Cardiovascular Aging.

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  Figure 2. Mechanisms and Monitoring of Cancer Therapy-Related Cardiovascular Aging (CTR-CVA). CTR-CVA is based on cellular senescence and involves six mechanisms: DNA damage and telomere deficiency, oxidative stress, upregulation of anti-apoptotic proteins, disruption of protein homeostasis, epigenetic modifications, and the senescence-associated secretory phenotype. In this review, the monitoring of CTR-CVA is categorized into biomarker-based monitoring, functional monitoring, and histological monitoring. CTR-CVA, Cancer Therapy-Related Cardiovascular Aging; ER, endoplasmic reticulum; mtDNA, mitochondrial DNA; SASP, senescence-associated secretory phenotype.

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  Figure 3. Cardiovascular Cellular Senescence Signaling during Chemotherapy and Radiotherapy. (A) Common Mechanisms of Cellular Senescence Induced by Chemotherapy and Radiotherapy: Both can induce DNA damage and abnormal repair, activating classical cellular senescence pathways such as the p53-p21 and p16-Rb pathways, which promotes cell-cycle arrest, leading cells to enter a state of cellular senescence; Both can induce oxidative stress related cellular senescence by activating the P38/MAPK-NFκB pathway or the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; Both can result in the secretion of various cytokines through pro-inflammatory reactions, causing the accumulation and spread of the senescence-associated secretory phenotype (SASP), thus inducing cellular senescence in adjacent cells; Both can increase the expression of anti-apoptotic proteins such as Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP) to counteract damage. Cells then enter a state of cellular senescence to avoid excessive apoptosis; Both can affect the mitochondrial oxidative respiratory chain, causing the accumulation of ROS within mitochondria, which exacerbates cellular senescence. (B)…