Gene expression profiling of hypoxic response in different models of senescent endothelial cells
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Endothelial cells senescence is a physiological process affecting vascular integrity. It can contribute to heart and arterial stiffening and remodeling, impaired angiogenesis, defective vascular repair, and with an increasing prevalence of atherosclerosis. Drugs used as antineoplastic therapies, targeting tumor as well as endothelial cells, can also trigger endothelial cells senescence. We demonstrated that a short pulse of axitinib, a specific inhibitor of vascular endothelial growth factor receptors, induces cell senescence of endothelial cells. Here, we performed a high-throughput gene expression analysis to characterize the response of proliferating versus senescent endothelial cells to hypoxia, the main trigger of neo-angiogenetic phenomena in tumors. We compared the response to hypoxia of replicative senescent cells, with that of axitinib or of DNA damage-induced senescence. Overall, we enlightened common and specific responses to different senescence inducers and changes in the Senescent Associated Secretory Phenotype.
KeywordsSenescence Endothelial cells Hypoxia RNAseq Axitinib Doxorubicin SASP
This work was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011) to AL and MLF.
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Maria Patrizia Mongiardi, Matilde Merolle and Valentina Fustaino. The first draft of the manuscript was written by Maria Laura Falchetti and Andrea Levi. All authors read and approved the final manuscript.
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Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Statement of human and animal rights
The experiments performed in the present manuscript do not envisage human subjects nor laboratory animals. The experiments were entirely carried on cell cultures.
For this type of study, formal consent is not required.