The role of mitofusin 2 in regulating endothelial cell senescence: Implications for vascular aging
Jiayin Li,
Zheming Yang,
Haixu Song,
Lin Yang,
Kun Na,
Zhu Mei,
Shuli Zhang,
Jing Liu,
Kai Xu,
Chenghui Yan,
Xiaozeng Wang
Affiliations
Jiayin Li
College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Zheming Yang
College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Haixu Song
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Lin Yang
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Kun Na
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Zhu Mei
College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Shuli Zhang
College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning 110167, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Jing Liu
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Kai Xu
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Chenghui Yan
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China
Xiaozeng Wang
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China; Corresponding author
Summary: 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 overexpression 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 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.
