动脉样硬化是一种由平滑肌肉细胞驱动的瘤状疾病
Huize Pan1,2, Sebastian E Ho1, Chenyi Xue1
1Division of Cardiology, Department of Medicine (H.P., S.E.H., C.X., J.C., Q.S.J., L.S.R., F.L., H.Z., M.P.R.), Columbia University Irving Medical Center, New York, NY.
Circulation
|April 30, 2024
概括
动脉样硬化涉及平滑肌肉细胞 (SMCs),表现得像瘤细胞一样,呈现基因组不稳定性和过度增殖. 用尼拉巴里布等药物准SMC转型显示出治疗这种心血管疾病的潜力.
科学领域:
- 心血管生物学
- 癌症生物学
- 翻译医学
背景情况:
- 动脉样硬化是心血管疾病的主要原因,由多种细胞类型的病态激活驱动.
- 平滑肌细胞 (SMC) 的表型转换越来越被认为是动脉样硬化发展和并发症的关键因素.
- 在疾病发病过程中,SMC衍生的细胞的确切性质和潜在机制尚不清楚.
研究的目的:
- 在动脉样硬化中描述SMC衍生细胞的瘤细胞类行为.
- 在动脉样硬化的背景下阐明驱动SMC过渡的机制.
- 探索针对SMC转型的新疗法,以预防和治疗动脉样硬化.
主要方法:
- 在小鼠中利用SMC血统追踪和人类组织分析.
- 采用多学科方法,包括分子,细胞,组织学,计算和遗传方法.
- 研究了瘤性Kras表达的影响,并测试了抗癌药物niraparib的疗效.
主要成果:
- 动脉样硬化中的SMC衍生细胞表现出类似瘤细胞的特征:基因组不稳定性,逃避衰老,超增殖,侵入性和与癌症相关的基因网络.
- 在SMC中表达瘤性KrasG12D会加速SMC转变并加剧动脉样硬化.
- 在小鼠模型中,DNA损伤修复抑制剂尼拉帕里布降低了动脉样硬化的进展,并诱导了病变的回归.
结论:
- 动脉样硬化可以被视为SMC驱动的,类似瘤的疾病,为其发病提供了新的见解.
- 这些发现为针对SMC转型的创新精确分子策略铺平了道路.
- 针对SMC转型为动脉样硬化心血管疾病提供了一个有前途的治疗途径.
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