CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal.
Cells. 2020 Sep 23;9(10):2146. doi: 10.3390/cells9102146.
Atherosclerosis is an age-related disorder associated with long-term exposure to cardiovascular risk factors. The asymptomatic progression of atherosclerotic plaques leads to major cardiovascular diseases (CVD), including acute myocardial infarctions or cerebral ischemic strokes in some cases. Senescence, a biological process associated with progressive structural and functional deterioration of cells, tissues and organs, is intricately linked to age-related diseases. Cell senescence involves coordinated modifications in cellular compartments and has been demonstrated to contribute to different stages of atheroma development. Senescence-based therapeutic strategies are currently being pursued to treat and prevent CVD in humans in the near-future. In addition, distinct experimental settings allowed researchers to unravel potential approaches to regulate anti-apoptotic pathways, facilitate excessive senescent cell clearance and eventually reverse atherogenesis to improve cardiovascular function. However, a deeper knowledge is required to fully understand cellular senescence, to clarify senescence and atherogenesis intertwining, allowing researchers to establish more effective treatments and to reduce the cardiovascular disorders' burden. Here, we present an objective review of the key senescence-related alterations of the major intracellular organelles and analyze the role of relevant cell types for senescence and atherogenesis. In this context, we provide an updated analysis of therapeutic approaches, including clinically relevant experiments using senolytic drugs to counteract atherosclerosis.
动脉粥样硬化是一种与长期暴露于心血管危险因素相关的与年龄相关的疾病。动脉粥样硬化斑块的无症状进展导致主要心血管疾病（CVD），在某些情况下包括急性心肌梗死或脑缺血性中风。衰老，与细胞、组织和器官的进行性结构和功能恶化相关的生物学过程，与与年龄相关的疾病密切相关。细胞衰老涉及细胞区室的协调修饰，并已被证明有助于动脉粥样硬化发展的不同阶段。目前正在研究基于衰老的治疗策略，以在不久的将来治疗和预防人类的 CVD。此外，不同的实验设置使研究人员能够揭示潜在的调节抗细胞凋亡途径、促进过度衰老细胞清除的方法，最终逆转动脉粥样硬化以改善心血管功能。然而，需要更深入的了解来充分理解细胞衰老，阐明衰老和动脉粥样硬化的交织，使研究人员能够建立更有效的治疗方法并减少心血管疾病的负担。在这里，我们对主要细胞内细胞器的关键衰老相关改变进行了客观的综述，并分析了相关细胞类型在衰老和动脉粥样硬化形成中的作用。在这种情况下，我们提供了治疗方法的最新分析，包括使用衰老细胞清除药物来对抗动脉粥样硬化的临床相关实验。
