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Updated: Jun 10, 2025
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
A preliminary study of sirtuin-1 on angiotensin II-induced senescence and inflammation in abdominal aortic aneurysms
Xiangyu Zhang1, Huanhuan Chen1, Tianshu Pang1
1Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Objective:
Recent evidence suggests the involvement of senescence and inflammation in abdominal aortic aneurysm (AAA). Considering the role of sirtuin-1 (SIRT1) in delaying senescence, we aimed to preliminarily investigate the potential mechanism underlying the effects of SIRT1 in senescence and inflammation during AAA.
Material And Methods:
A cell AAA model was established using angiotensin II (Ang II) as the inducer, which was applied to treat human aortic vascular smooth muscle cells (HASMCs). The senescence and cell cycle of treated HASMCs were evaluated based on senescence-associated (SA)-b-galactosidase (b-gal) assay and flow cytometry, respectively. The levels of inflammatory cytokines and proteins related to senescence-associated secretory phenotype (SASP), along with nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinases (MAPK) pathways, as well as SIRT1, were gauged. The correlation between SIRT1 and NF-kB and MAPK pathway-related proteins was further estimated.
Results:
In Ang II-treated HASMCs, reduced SIRT1 and B-cell lymphoma-2 levels yet increased levels of SASP-related proteins P16 and P21, inflammatory cytokines, as well as Bax and caspases were all visible. In the meantime, Ang II exposure enhanced the number of b-gal-positive HASMCs and promoted cell cycle arrest. SIRT1 was also repressed following Ang II treatment and negatively correlated with NF-kB and MAPK pathway-related proteins (P < 0.05). Furthermore, the overexpression of SIRT1 diminished the levels of SASP-related proteins and reduced the phosphorylation of extracellular regulated kinase 1/2 and P65 in Ang II-treated HASMCs (P < 0.05).
Conclusion:
Taken together, our results indicate that SIRT1 overexpression attenuates the inflammatory and senescent responses of HASMCs in the Ang II-induced AAA cell model. This finding suggests that SIRT1 can be a highly promising target for clinical treatment of AAA.
