Programmed cell death-related ABI1 is a critical mediator of abdominal aortic aneurysm

Eur J Med Res. 2024 Nov 21;29(1):557. doi: 10.1186/s40001-024-02128-4.

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by localized dilation of the abdominal aorta, posing a significant risk of rupture and fatal hemorrhage. While surgical and endovascular repair techniques have advanced, the underlying mechanisms driving AAA development remain unclear, hindering the development of effective preventive and therapeutic strategies. Using bioinformatics analysis of publicly available data sets, the study identified a strong correlation between cell death (CD) score and different types of programmed cell death scores in AAA samples. WGCNA analysis revealed a module enriched in genes related to proteasome-mediated protein degradation, nuclear envelope, and endocytosis, significantly correlated with CD score. Further analysis identified ABI1 as a dominant feature gene, highlighting its potential role in AAA pathogenesis. In vitro validation using an Angiotensin II-induced AAA model in human aortic smooth muscle cells demonstrated that siRNA-mediated knockdown of ABI1 significantly reduced cell apoptosis, migration, and the expression of pro-apoptotic proteins, confirming ABI1's crucial role in promoting CD and AAA progression. The findings suggest that ABI1 may represent a promising therapeutic target for the prevention and treatment of AAA. Further research is warranted to fully understand the role of ABI1 in AAA and to develop targeted therapies based on this promising target.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Angiotensin II / metabolism
  • Aortic Aneurysm, Abdominal* / genetics
  • Aortic Aneurysm, Abdominal* / metabolism
  • Aortic Aneurysm, Abdominal* / pathology
  • Apoptosis* / genetics
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Angiotensin II