Lambert Jordi, Jørgensen Helle F
Section of Cardiorespiratory Medicine, University of Cambridge, VPD Heart and Lung Research Institute, Papworth Road, Cambridge Biomedical Campus, Cambridge, CB2 0BB, UK.
Atherosclerosis. 2025 Feb;401:119085. doi: 10.1016/j.atherosclerosis.2024.119085. Epub 2024 Dec 10.
Vascular smooth muscle cells (VSMCs) in adult arteries maintain substantial phenotypic plasticity, which allows for the reversible cell state changes that enable vascular remodelling and homeostasis. In atherosclerosis, VSMCs dedifferentiate in response to lipid accumulation and inflammation, resulting in loss of their characteristic contractile state. Recent studies showed that individual, pre-existing VSMCs expand clonally and can acquire many different phenotypes in atherosclerotic lesions. The changes in gene expression underlying this phenotypic diversity are mediated by epigenetic modifications which affect transcription factor access and thereby gene expression dynamics. Additionally, epigenetic mechanisms can maintain cellular memory, potentially facilitating reversion to the contractile state. While technological advances have provided some insight, a comprehensive understanding of how VSMC phenotypes are governed in disease remains elusive. Here we review current literature in light of novel insight from studies at single-cell resolution. We also discuss how lessons from epigenetic studies of cellular regulation in other fields could help in translating the potential of targeting VSMC phenotype conversion into novel therapies in cardiovascular disease.
成年动脉中的血管平滑肌细胞（VSMCs）保持着显著的表型可塑性，这使得细胞状态能够可逆性改变，从而实现血管重塑和体内平衡。在动脉粥样硬化中，VSMCs会因脂质积累和炎症而发生去分化，导致其特征性收缩状态丧失。最近的研究表明，单个已存在的VSMCs会进行克隆性扩增，并在动脉粥样硬化病变中获得许多不同的表型。这种表型多样性背后的基因表达变化是由表观遗传修饰介导的，表观遗传修饰会影响转录因子的结合，进而影响基因表达动态。此外，表观遗传机制可以维持细胞记忆，潜在地促进细胞恢复到收缩状态。尽管技术进步提供了一些见解，但对于疾病中VSMC表型是如何被调控的，仍缺乏全面的了解。在此，我们根据单细胞分辨率研究的新见解，对当前文献进行综述。我们还将讨论，从其他领域细胞调控的表观遗传学研究中获得的经验教训，如何有助于将靶向VSMC表型转化的潜力转化为心血管疾病的新型疗法。
