GSDME-依赖性热死驱动腹腔大动脉动脉瘤通过促进血管衰老
Si-Jia Sun1,2, Zhen Zhang1, Guo-Yan Zhang1
1Department of Pharmacy, Shanghai Tenth People's Hospital Affiliated to School of Medicine of Tongji University, Shanghai, China.
Nature communications
|December 17, 2025
概括
加斯德明-E (GSDME) 触发了血管衰老和腹腔大动脉瘤 (AAA) 的进展. 在血管光滑肌细胞中抑制GSDME显示了AAA治疗的潜力.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 免疫学 免疫学 免疫学
背景情况:
- 衰老与腹腔大动脉动脉瘤 (AAA) 病理有关.
- 在AAA中调节衰老的机制尚未完全理解.
研究的目的:
- 在AAA中调查气体皮质胺-E (GSDME) 依赖的非正规性热的作用.
- 探索GSDME作为AAA的潜在治疗点.
主要方法:
- 对AAA小鼠模型和患者样本的分析.
- 单细胞RNA测序 (scRNA-seq) 和散装RNA-seq. 这两种测序方法是:
- 多重流细胞计. 多重流细胞计.
- GSDME基因删除和重新引入研究.
- 使用达沙替尼加奎尔塞丁的老化疗法.
主要成果:
- 在AAA血管壁中,GSDME依赖性热是活跃的.
- 缺乏GSDME会减少血管衰老和AAA的进展.
- 在AAA中,GSDME驱动VSMC重编程并改变免疫细胞概况.
- 在VSMC中重新引入GSDME,但不是髓状细胞,恢复AAA表型.
- 老化疗法废除了GSDME诱导的AAA.
结论:
- 在VSMC中,GSDME依赖性热的作用是AAA病变发生的关键调节器 ("主开关").
- 针对VSMC中的GSDME为AAA提供了一个有前途的治疗策略.
相关概念视频
Peripheral Artery Disease I: Introduction
288
Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
288
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
Aneurysm I: Introduction
304
An aortic aneurysm is a localized outpouching or dilation at a weak point in the artery wall. It may involve different parts of the aorta, such as the abdominal aorta, aortic arch, or thoracic aorta.Etiological factorsSeveral disorders are associated with aortic aneurysms.Congenital causes, such as primary connective tissue disorders like Marfan syndrome, impact the integrity and strength of connective tissues, notably affecting the aorta. Marfan syndrome is a genetic disorder that specifically...
304


