A preliminary study of sirtuin-1 on angiotensin II-induced senescence and inflammation in abdominal aortic aneurysms.

IF 2.5 4区医学 Q2 PATHOLOGY

Cytojournal Pub Date : 2024-09-27 eCollection Date: 2024-01-01 DOI:10.25259/Cytojournal_80_2024

Xiangyu Zhang, Huanhuan Chen, Tianshu Pang, Kai Liang, Jinhua Mei, Yuefeng Zhu, Jin Yang

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引用次数: 0

Abstract

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.

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sirtuin-1对血管紧张素II诱导的腹主动脉瘤衰老和炎症的初步研究。

目的：最近的证据表明，衰老和炎症参与了腹主动脉瘤（AAA）。考虑到sirtuin-1（SIRT1）在延缓衰老中的作用，我们旨在初步研究SIRT1在AAA过程中影响衰老和炎症的潜在机制：以血管紧张素II（Ang II）为诱导剂，建立了细胞AAA模型，并应用该诱导剂处理人主动脉血管平滑肌细胞（HASMCs）。根据衰老相关（SA）-b-半乳糖苷酶（b-gal）检测法和流式细胞术分别评估了处理过的 HASMCs 的衰老和细胞周期。此外，还检测了炎性细胞因子和与衰老相关分泌表型（SASP）有关的蛋白质、核因子-卡巴B（NF-kB）和丝裂原活化蛋白激酶（MAPK）通路以及 SIRT1 的水平。结果发现，在 Ang II 处理的 HAS 细胞中，SIRT1 与 NF-kB 和 MAPK 通路相关蛋白之间的相关性得到了进一步估测：结果：在经 Ang II 处理的 HASMCs 中，可以看到 SIRT1 和 B 细胞淋巴瘤-2 水平降低，而 SASP 相关蛋白 P16 和 P21、炎症细胞因子以及 Bax 和 caspases 水平升高。同时，暴露于 Ang II 会增加 b-gal 阳性 HASMC 的数量，并促进细胞周期停滞。SIRT1 也在 Ang II 处理后受到抑制，并与 NF-kB 和 MAPK 通路相关蛋白呈负相关（P < 0.05）。此外，在 Ang II 处理的 HASMCs 中，SIRT1 的过表达降低了 SASP 相关蛋白的水平，并减少了细胞外调控激酶 1/2 和 P65 的磷酸化（P < 0.05）：综上所述，我们的研究结果表明，在 Ang II 诱导的 AAA 细胞模型中，SIRT1 的过表达可减轻 HASMCs 的炎症和衰老反应。这一研究结果表明，SIRT1 可能是临床治疗 AAA 的一个极具前景的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.