ATP酸酶通过代谢和表观遗传变化驱动系统和肺血管疾病的血管重塑
Yann Grobs1, Charlotte Romanet1, Sarah-Eve Lemay1
1Pulmonary Hypertension Research Group, Québec Heart and Lung Institute Research Centre, Québec City, QC G1V 4G5, Canada.
Science translational medicine
|December 11, 2024
概括
抑制ATP酸酶 (ACLY) 减少了血管光滑肌肉细胞的增殖和迁移,为冠状动脉疾病和肺动脉高血压等血管疾病提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 血管生物学 血管生物学
- 分子医学是分子医学.
背景情况:
- 酸酶 (ACLY) 是脂质合成和基因素乙化的组成部分.
- ACLY调节血管光滑肌细胞 (VSMC) 的增殖和生存.
- 在与心血管疾病相关的血管改造中,ACLY表达升高.
研究的目的:
- 为了研究ACLY在血管改造中的作用.
- 评估ACLY作为血管疾病的治疗点.
主要方法:
- 在人体血管组织中检查了ACLY表达.
- 在培养的人类VSMC和动物模型中药理和遗传上抑制了ACLY.
- 评估了细胞增殖,迁移,细胞亡,糖溶解,脂质合成和基因素乙化.
- 使用的动脉损伤,苏根/低氧模型和ex vivo人类组织模型.
主要成果:
- 抑制ACLY可以减少VSMC的扩散,迁移和增加亡.
- 抑制降低了葡萄糖分解,脂质合成,GCN5依赖的基因素乙化和FOXM1的表达.
- 在动物模型和人类ex vivo系统中,ACLY抑制缓解了血管重塑.
结论:
- 在血管重塑和疾病进展中,ACLY起着至关重要的作用.
- 针对ACLY是一个有前途的治疗策略,用于血管疾病.
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