SIRT6-mediated vascular smooth muscle cells senescence participates in the pathogenesis of abdominal aortic aneurysm

Atherosclerosis. 2024 May:392:117483. doi: 10.1016/j.atherosclerosis.2024.117483. Epub 2024 Feb 24.

Abstract

Background and aims: In this study, we carried out a clinical sample study, and in vivo and in vitro studies to evaluate the effect of SIRT6 and SIRT6-mediated vascular smooth muscle senescence on the development of abdominal aortic aneurysm (AAA).

Method and results: AAA specimen showed an increased P16, P21 level and a decreased SIRT6 level compared with control aorta. Time curve study of Ang II infusion AAA model showed similar P16, P21 and SIRT6 changes at the early phase of AAA induction. The in vivo overexpression of SIRT6 significantly prevented AAA formation in Ang II infusion model. The expression of P16 and P21 was significantly reduced after SIRT6 overexpression. SIRT6 overexpression also attenuated chronic inflammation and neo-angiogenesis in Ang II infusion model. The overexpression of SIRT6 could attenuate premature senescence, inflammatory response and neo-angiogenesis in human aortic smooth muscle cells (HASMC) under Ang II stimulation.

Conclusions: SIRT6 overexpression could limit AAA formation via attenuation of vascular smooth muscle senescence, chronic inflammation and neovascularity.

Keywords: Abdominal aortic aneurysm; Cell senescence; Chronic inflammation; SIRT6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II*
  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal* / metabolism
  • Aortic Aneurysm, Abdominal* / pathology
  • Cells, Cultured
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Muscle, Smooth, Vascular* / metabolism
  • Muscle, Smooth, Vascular* / pathology
  • Myocytes, Smooth Muscle* / metabolism
  • Myocytes, Smooth Muscle* / pathology
  • Neovascularization, Pathologic
  • Sirtuins* / genetics
  • Sirtuins* / metabolism

Substances

  • Sirtuins
  • SIRT6 protein, human
  • Angiotensin II
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Sirt6 protein, mouse
  • CDKN2A protein, human
  • CDKN1A protein, human