Short- and Long-Term Endothelial Inflammation Have Distinct Effects and Overlap with Signatures of Cellular...

Area of Science:

• Endothelial cell biology
• Cellular senescence
• Inflammation research

Background:

• Cellular senescence and inflammation are implicated in aging and disease.
• Endothelial cells play a crucial role in cardiovascular health.
• The interplay between senescence and inflammation in endothelial cells requires further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the interplay between cellular senescence and inflammation in human umbilical vein endothelial cells (HUVECs).
• To compare gene expression profiles of senescent HUVECs with those under acute or chronic TNFα-mediated inflammation.
• To validate key molecular and functional changes associated with senescence and inflammation.

Main Methods:

• Induction of replicative and radiation-stress-induced senescence in HUVECs.
• RNA sequencing to analyze gene expression changes.
• Experimental validation of gene expression and functional assays (proliferation, cytokine secretion, wound healing).

Main Results:

• Both senescence and chronic inflammation induced upregulation of genes related to endothelial-mesenchymal transition (EMT) and inflammatory pathways.
• Chronic inflammation showed a pronounced EMT signature, while acute inflammation activated classical inflammatory responses.
• Senescent and chronically inflamed cells exhibited reduced proliferation, increased IL-6/IL-8 secretion, and impaired wound healing.

Conclusions:

• Cellular senescence and inflammation share common molecular pathways, including EMT and inflammatory signaling, in HUVECs.
• Inflammation exacerbates senescence-associated changes, contributing to endothelial dysfunction.
• Findings provide insights into age-related cardiovascular pathologies and potential therapeutic targets.