With old age, everyone develops atherosclerosis, a condition characterized by the formation and growth of fatty plaques that narrow and weaken blood vessels. The more cholesterol present in an atherosclerotic plaque, the softer the plaque structure, and the greater the likelihood of fragmentation and rupture leading to a heart attack or stroke. Local excesses of cholesterol cause cell dysfunction, and in plaque this is particularly important in the macrophages that arrive to attempt to return excess cholesterol to the blood stream and otherwise repair the local damage. Instead of conducting repair, the cells instead become dysfunction and inflammatory. Many become senescent cells, and there is compelling evidence for the presence of senescent cells to make the dysfunction in plaque worse.
Recently, cellular senescence-induced unstable carotid plaques have gained increasing attention. In this study, we utilized bioinformatics and machine learning methods to investigate the correlation between cellular senescence and the pathological mechanisms of unstable carotid plaques. Our aim was to elucidate the causes of unstable carotid plaque progression and identify new therapeutic strategies. First, differential expression analysis was performed on a test set to identify differentially expressed genes (DEGs) between the unstable plaque group and the control group. These DEGs were intersected with cellular senescence-associated genes to obtain 40 cellular senescence-associated (CSA)-DEGs.
First, we investigated the expression and function of CSA-DEGs in unstable carotid plaques. The expression of CSA-DEGs in cells from unstable carotid plaques differed significantly from the control group. These genes are mainly related to cellular senescence, apoptosis, cell proliferation regulation, and inflammatory response. Typically, the characteristics of cellular senescence are described as irreversible proliferation arrest and senescence-associated secretory phenotype (SASP). Additionally, these genes are involved in pathways such as the MAPK signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. These pathways play crucial roles in the aging process, and their dysregulation is closely associated with the progression of unstable carotid plaques. Interestingly, we also observed that CSA-DEGs are closely related to T lymphocyte proliferation and cellular immunity, which is consistent with previous studies.
Link: https://doi.org/10.1038/s41598-024-78251-3
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