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. siMFN2 treatment worsened Ang II-induced senescence, while MFN2 over- expression alleviated it. siMFN2 or Ang II treatment caused mitochondrial dysfunction and morphological abnormalities, including increased ROS production and reduced respiration, mitigated by ovMFN2 treatment. Further study revealed that BCL6, a negative regulator of MFN2, significantly contributes to Ang II- induced endothelial senescence. In vivo, , Ang II infusion decreased MFN2 expression and increased BCL6, P21, and P53 expression in vascular endothelial cells. The shMfn2+Ang +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.