Department of Surgery, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Location VU Medical Center and AMC, Amsterdam, The Netherlands.
Department of Physiology, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Location VU Medical Center, Amsterdam, The Netherlands.
Eur J Clin Invest. 2022 Apr;52(4):e13697. doi: 10.1111/eci.13697. Epub 2021 Nov 21.
Aortic aneurysms (AA) are pathological dilations of the aorta, associated with an overall mortality rate up to 90% in case of rupture. In addition to dilation, the aortic layers can separate by a tear within the layers, defined as aortic dissections (AD). Vascular smooth muscle cells (vSMC) are the predominant cell type within the aortic wall and dysregulation of vSMC functions contributes to AA and AD development and progression. However, since the exact underlying mechanism is poorly understood, finding potential therapeutic targets for AA and AD is challenging and surgery remains the only treatment option.
In this review, we summarize current knowledge about vSMC functions within the aortic wall and give an overview of how vSMC functions are altered in AA and AD pathogenesis, organized per anatomical location (abdominal or thoracic aorta).
Important functions of vSMC in healthy or diseased conditions are apoptosis, phenotypic switch, extracellular matrix regeneration and degradation, proliferation and contractility. Stressors within the aortic wall, including inflammatory cell infiltration and (epi)genetic changes, modulate vSMC functions and cause disturbance of processes within vSMC, such as changes in TGF-β signalling and regulatory RNA expression.
This review underscores a central role of vSMC dysfunction in abdominal and thoracic AA and AD development and progression. Further research focused on vSMC dysfunction in the aortic wall is necessary to find potential targets for noninvasive AA and AD treatment options.
主动脉瘤（AA）是主动脉的病理性扩张，破裂时总体死亡率高达 90%。除了扩张，主动脉层也可能因层内撕裂而分离，这种情况被定义为主动脉夹层（AD）。血管平滑肌细胞（vSMC）是主动脉壁中的主要细胞类型，vSMC 功能的失调导致 AA 和 AD 的发生和发展。然而，由于确切的潜在机制尚不清楚，因此寻找 AA 和 AD 的潜在治疗靶点具有挑战性，手术仍然是唯一的治疗选择。
在这篇综述中，我们总结了 vSMC 在主动脉壁中的功能的现有知识，并概述了 vSMC 在 AA 和 AD 发病机制中的功能是如何改变的，按解剖位置（腹主动脉或胸主动脉）进行组织。
vSMC 在健康或患病条件下的重要功能包括细胞凋亡、表型转换、细胞外基质的再生和降解、增殖和收缩性。主动脉壁内的应激源，包括炎症细胞浸润和（表观）遗传改变，调节 vSMC 的功能并导致 vSMC 内过程的紊乱，如 TGF-β信号和调节 RNA 表达的变化。
本综述强调了 vSMC 功能障碍在腹主动脉和胸主动脉 AA 和 AD 发生和发展中的核心作用。需要进一步研究主动脉壁中 vSMC 功能障碍，以寻找非侵入性 AA 和 AD 治疗方法的潜在靶点。
