AGEs induce endothelial cells senescence and endothelial barrier dysfunction via miR-1-3p/MLCK signaling pathways

Area of Science:

• Vascular Biology
• Cellular Senescence
• Molecular Medicine

Background:

• Advanced glycation end products (AGEs) impair endothelial barrier function, contributing to vascular aging.
• MicroRNAs (miRNAs) are emerging as therapeutic targets for age-related vascular disorders.
• Understanding miRNA regulation in AGEs-induced endothelial dysfunction is crucial.

Purpose of the Study:

• To investigate the impact of AGEs on endothelial cell senescence and barrier integrity in human umbilical vein endothelial cells (HUVECs).
• To explore the role of microRNA-1-3p (miR-1-3p) in mediating AGEs-induced endothelial dysfunction.
• To assess the therapeutic potential of miR-1-3p overexpression in counteracting AGEs effects.

Main Methods:

• HUVECs were exposed to AGEs and transfected with miR-1-3p mimics.
• Endothelial senescence was evaluated using senescence-associated β-galactosidase (SA-β-Gal) staining and senescence markers (P53, P21, P16).
• Endothelial barrier function was assessed by measuring transendothelial electric resistance (TEER) and analyzing myosin light chain kinase (MLCK) signaling pathway components.

Main Results:

• AGEs significantly induced endothelial cell senescence, evidenced by increased SA-β-Gal staining and elevated P53, P21, and P16 expression.
• AGEs impaired endothelial barrier function, decreasing TEER and increasing MLCK signaling and related proteins.
• miR-1-3p levels were reduced by AGEs; miR-1-3p overexpression reversed AGEs-induced barrier dysfunction, oxidative stress, and senescence by downregulating MLCK.

Conclusions:

• AGEs induce endothelial cell senescence and barrier dysfunction through the miR-1-3p/MLCK signaling pathway.
• miR-1-3p acts as a protective factor against AGEs-induced endothelial damage.
• Targeting the miR-1-3p/MLCK pathway offers a potential therapeutic strategy for age-related vascular diseases.