Lin Alexander, Miano Joseph M, Fisher Edward A, Misra Ashish
Atherosclerosis and Vascular Remodelling Group, Heart Research Institute, Sydney, New South Wales, Australia.
School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, New South Wales, Australia.
Nat Cardiovasc Res. 2024 Dec;3(12):1408-1423. doi: 10.1038/s44161-024-00569-y. Epub 2024 Dec 9.
Vascular smooth muscle cells, endothelial cells and macrophages undergo phenotypic conversions throughout atherosclerosis progression, both as a consequence of chronic inflammation and as subsequent drivers of it. The inflammatory hypothesis of atherosclerosis has been catapulted to the forefront of cardiovascular research as clinical trials have shown that anti-inflammatory therapy reduces adverse cardiovascular events. However, no current therapies have been specifically designed to target the phenotype of plaque cells. Fate mapping has revealed that plaque cells convert to detrimental and beneficial cell phenotypes during atherosclerosis, with cumulative evidence highlighting that vascular cell plasticity is intimately linked with plaque inflammation, ultimately impacting lesion stability. Here we review vascular cell plasticity during atherosclerosis in the context of the chronic inflammatory plaque microenvironment. We highlight the need to better understand how plaque cells behave during therapeutic intervention. We then propose modulating plaque cell phenotype as an unexplored therapeutic paradigm in the clinical setting.
在动脉粥样硬化进展过程中，血管平滑肌细胞、内皮细胞和巨噬细胞会发生表型转变，这既是慢性炎症的结果，也是其后续驱动因素。动脉粥样硬化的炎症假说已成为心血管研究的前沿领域，因为临床试验表明抗炎治疗可减少不良心血管事件。然而，目前尚无专门针对斑块细胞表型的疗法。命运图谱显示，在动脉粥样硬化过程中，斑块细胞会转变为有害和有益的细胞表型，越来越多的证据表明血管细胞可塑性与斑块炎症密切相关，最终影响病变稳定性。在此，我们在慢性炎症斑块微环境的背景下综述动脉粥样硬化过程中的血管细胞可塑性。我们强调需要更好地了解治疗干预期间斑块细胞的行为。然后，我们提出调节斑块细胞表型作为临床环境中一种未被探索的治疗模式。
