Transcriptional activation of genes associated with the matrisome is a common feature of senescent endothelial cells.

Abstract

Cellular senescence is a stable cell cycle arrest that occurs in response to various stress stimuli and affects multiple cell types, including endothelial cells (ECs). Senescent cells accumulate with age, and their removal has been linked to reduced age-related diseases. However, some senescent cells are important for tissue homeostasis. Therefore, understanding the diversity of senescent cells in a cell-type-specific manner and their underlying molecular mechanisms is essential. Senescence impairs key ECs functions which are necessary for vascular homeostasis, leading to endothelial dysfunction and age-related vascular diseases. In order to gain insights into these mechanisms, we analyzed publicly available RNA-seq datasets to identify gene expression changes in senescent ECs induced by doxorubicin, irradiation, and replication exhaustion. While only a few genes were consistently differentially expressed across all conditions, some gene ontologies (GO) were shared. Among these, our analysis focused on validating the expression of genes associated with the matrisome, which includes genes encoding for extracellular matrix (ECM) structural components and ECM-associated proteins, in a doxorubicin-induced senescence model. Our results show that the matrisome transcriptome undergoes significant remodeling in senescent endothelial cells, regardless of the specific inducers of senescence, highlighting the importance of understanding how ECM alterations affect senescence.