Smooth muscle cells in atherosclerosis: clones but not carbon copies.
Smooth muscle cells in atherosclerosis: clones but not carbon copies.
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DOI：
10.1016/j.jvssci.2021.02.002
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Gomez D
中科院分区：
文献类型：
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作者：
Espinosa-Diez C;Mandi V;Du M;Liu M;Gomez D
在过去的十年中，随着技术的发展，我们对血管平滑肌细胞(SMC)在动脉粥样硬化中的作用的认识有了很大的进步，使得我们能够明确地识别和表征病变血管壁内的SMC群体。通过进行命运图谱或单细胞转录学研究，或两者的组合，该领域已经做出了关键观察：SMC通过选择性地扩张和投资有限数量的内侧SMC来填充动脉粥样硬化病变，这些SMC经历了对其原始表型和功能的深刻和多样化的改变。因此，如果位于动脉粥样硬化病变内并导致疾病的SMC是克隆的，它们就不是碳拷贝，可以发挥动脉粥样硬化保护或促进动脉粥样硬化的作用，这取决于它们表型转换的性质。在确定影响SMC命运的转录机制方面已经取得了巨大的进展。本文综述了近年来在动脉粥样硬化病变中SMC投资和表型多样性的特征以及控制SMC命运的分子机制方面的研究进展。我们还讨论了与这些突破性观测相关的一些剩余问题。这些问题包括：调控SMC寡克隆扩张现象的潜在机制；单细胞转录是否可靠和足以确定SMC在动脉粥样硬化发生和发展过程中的功能和贡献；SMC克隆性和表型可塑性如何影响翻译研究和为预防动脉粥样硬化并发症而开发的治疗方法。最后，我们讨论了该领域应该倾向于的互补方法，结合单细胞表型分类和功能研究，进一步了解复杂的SMC行为和在动脉粥样硬化中的作用。
Our knowledge of the contribution of vascular smooth muscle cells (SMCs) to atherosclerosis has greatly advanced in the previous decade with the development of techniques allowing for the unambiguous identification and phenotypic characterization of SMC populations within the diseased vascular wall. By performing fate mapping or single-cell transcriptomics studies, or a combination of both, the field has made key observations: SMCs populate atherosclerotic lesions by the selective expansion and investment of a limited number of medial SMCs, which undergo profound and diverse modifications of their original phenotype and function. Thus, if SMCs residing within atherosclerotic lesions and contributing to the disease are clones, they are not carbon copies and can play atheroprotective or atheropromoting roles, depending on the nature of their phenotypic transitions. Tremendous progress has been made in identifying the transcriptional mechanisms biasing SMC fate. In the present review, we have summarized the recent advances in characterizing SMC investment and phenotypic diversity and the molecular mechanisms controlling SMC fate in atherosclerotic lesions. We have also discussed some of the remaining questions associated with these breakthrough observations. These questions include the underlying mechanisms regulating the phenomenon of SMC oligoclonal expansion; whether single-cell transcriptomics is reliable and sufficient to ascertain SMC functions and contributions during atherosclerosis development and progression; and how SMC clonality and phenotypic plasticity affects translational research and the therapeutic approaches developed to prevent atherosclerosis complications. Finally, we have discussed the complementary approaches the field should lean toward by combining single-cell phenotypic categorization and functional studies to understand further the complex SMC behavior and contribution in atherosclerosis.