The role of mitofusin 2 in regulating endothelial cell senescence: Implications for vascular aging.

Endothelial cell dysfunction contributes to age-related vascular diseases. Analyzing public databases and mouse tissues, we found decreased MFN2 expression in senescent endothelial cells and angiotensin II-treated mouse aortas. In human endothelial cells, Ang II reduced MFN2 expression while increasing senescence markers P21 and P53. treatment worsened Ang II-induced senescence, while MFN2 overexpression alleviated it. or Ang II treatment caused mitochondrial dysfunction and morphological abnormalities, including increased ROS production and reduced respiration, mitigated by treatment. Further study revealed that BCL6, a negative regulator of MFN2, significantly contributes to Ang II-induced endothelial senescence. , Ang II infusion decreased MFN2 expression and increased BCL6, P21, and P53 expression in vascular endothelial cells. The +Ang II group showed elevated senescence markers in vascular tissues. These findings highlight MFN2's regulatory role in endothelial cell senescence, emphasizing its importance in maintaining endothelial homeostasis and preventing age-related vascular diseases.