Background
The global population of older individuals is growing, and ageing is a key risk factor for atherosclerotic cardiovascular diseases. Abnormal accumulation of senescent cells can cause potentially deleterious effects on the organism with age. As a vital marker of cellular senescence, the senescence-associated secretory phenotype (SASP) is a novel mechanism to link cellular senescence with atherosclerosis.
Main body
In this review, we concretely describe the characteristics of the SASP and its regulation mechanisms. Importantly, we provide novel perspectives on how the SASP can promote atherosclerosis. The SASP from different types of senescent cells have vital roles in atherosclerosis progression. As a significant mediator of the harmful effects of senescent cells, it can play a pro-atherogenic role by producing inflammation and immune dysfunction. Furthermore, the SASP can deliver senescence signals to the surrounding vascular cells, gradually contributing to the development of atherosclerosis. Finally, we focus on a variety of novel therapeutic strategies aimed to reduce the burden of atherosclerosis in elderly individuals by targeting senescent cells and inhibiting the regulatory mechanisms of the SASP.
Conclusion
This review systematically summarizes the multiple roles of the SASP in atherosclerosis and can contribute to the exploration of new therapeutic opportunities.
Background/Aims: Bleomycin is a clinically used anti-cancer drug that produces DNA breaks once inside of cells. However, bleomycin is a positively charged molecule and cannot get inside of cells by free diffusion. We previously reported that the cell surface negatively charged glycosaminoglycans (GAGs) may be involved in the cellular uptake of bleomycin. We also observed that a class of positively charged small molecules has Golgi localization once inside of the cells. We therefore hypothesized that bleomycin might perturb Golgi-operated GAG biosynthesis. Methods: We used stable isotope labeling coupled with LC/MS analysis of GAG disaccharides simultaneously from bleomycin-treated and non-treated cancer cells. To further understand the cytotoxicity of bleomycin and its relationship to GAGs, we used sodium chlorate to inhibit GAG sulfation and commercially available GAGs to compete for cell surface GAG/bleomycin interactions in seven cell lines including CHO745 defective in both heparan sulfate and chondroitin sulfate biosynthesis. Results: we discovered that heparan sulfate GAG was significantly undersulfated and the quantity and disaccharide compositions of GAGs were changed in bleomycin-treated cells in a concentration- and time-dependent manner. We revealed that bleomycin-induced cytotoxicity was directly related to cell surface GAGs. Conclusion: GAGs were targeted by bleomycin both at cell surface and at Golgi. Thus, GAGs might be the biological relevant molecules that might be related to the bleomycin-induced fibrosis in certain cancer patients, a severe side effect with largely unknown molecular mechanism.
How do unique objects affect multiple-object tracking? Recent research has catalogued seemingly contradictory findings, varying from enhanced to impaired tracking performance. In this study, we explore the role of object complexity in this broad range of phenomena. In a series of three experiments, we demonstrate that unique objects of varying complexity can produce both costs and benefits on tracking performance. These experiments show that the key effects of uniqueness in object tracking are results of a tradeoff between tracking operation and processing of object identity information within the capacity limit of working memory.
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