通过激活通过激素乙化诱导的Notch信号来逆转大动脉细胞化
Gloria Garoffolo1, Silvia Ferrari1, Sara De Martino2
1Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Signal transduction and targeted therapy
|September 17, 2025
概括
一项新的研究将大动脉结石化与细胞衰老和表观遗传变化联系在一起. 一种新的治疗方法SPV106在细胞中逆转了这些影响,并在动物模型中减少了化,为门狭窄症治疗提供了希望.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞衰老 细胞衰老
背景情况:
- 大动脉的化在老年人群中很常见,但人们对其了解甚少.
- 目前对门化的治疗方法有限,这凸显了大量未满足的医疗需求.
- 这项研究调查了细胞衰老和表观遗传改变在大动脉结石化中的作用.
研究的目的:
- 为了检查细胞衰老,表观遗传修饰和人类膜间歇细胞 (VICs) 中的化之间的关联.
- 评估SPV106的治疗潜力,一个基酸转移酶激活剂,在逆转衰老和性VIC表型.
- 在ex vivo和in vivo模型中评估SPV106在预防和治疗大动脉结石化的疗效.
主要方法:
- 在人类VIC中检查了表观遗传标记 (DNA甲基化,基因素乙化/甲基化),衰老和化,这些标记来自患有大动脉缺陷和狭窄症的患者.
- 使用了由维生素D给药诱导的血管/膜化的小鼠模型.
- 用Pentadecylidenemalonate-1b (SPV106) 治疗人类VIC和小鼠模型,以激活KAT2B/pCAF基因组酸转移酶.
主要成果:
- 经历化的人类VICs表现出老化的表型,DNA甲基化增加和基因组表观遗传标记改变.
- 在人体VIC中,SPV106治疗恢复了基因素乙化,改变了染色质的可访问性,并上调了Notch1的表达.
- SPV106防止了性损伤的积累ex vivo和减少了膜化,保持了膜运动,并在体内改善了心脏功能.
结论:
- 细胞衰老和表观遗传变化与大动脉结石化有关.
- SPV106,通过激活基因组乙转移酶,可以逆转衰老/性VIC表型.
- 希斯乙转移酶激活剂代表了一种有前途的治疗策略,用于预防和治疗大动脉狭窄.
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