Cell-specific role of apoptosis in the process of atherosclerosis

Kanavos, Theofilos*,#; Birbas, Effrosyni

Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA

*Correspondence to: Theofilos Kanavos, MD, tkanavos@northwell.edu.

Abstract

Atherosclerosis is a chronic disease of the arterial wall characterized by the accumulation of fatty and fibrous material in the intima. It is the primary cause of cardiovascular disease, which is associated with high mortality and morbidity rates, particularly in aging populations. Apoptosis is a tightly regulated form of programmed cell death that eliminates unneeded or harmful cells. Its role in the process of atherosclerosis has been the subject of numerous recent studies. In this context, the impact of apoptosis on atherosclerosis was comprehensively examined through a narrative literature review. The effect of apoptosis on atherosclerosis depends on the cell types involved and the stage of the disease. Endothelial cell apoptosis, exacerbated by aging, may disrupt the integrity of the vascular lining and thereby facilitate the infiltration of lipids into the subendothelial space and promote plaque vulnerability. Evidence suggests that apoptosis of vascular smooth muscle cells can inhibit their migration and proliferation and attenuate plaque formation in early atherosclerosis but also induce plaque instability by thinning the fibrous cap in the advanced stages of the disease. Macrophage apoptosis plays a dual role in atherosclerosis depending on its timing as it can limit lesion cellularity and suppress plaque progression in the initial stages while exacerbating necrotic core development and plaque vulnerability in the late stages. Although more studies are required to fully elucidate the role of apoptosis in atherosclerosis, its therapeutic manipulation appears to be a promising strategy for addressing this multifactorial disease.

凋亡在动脉粥样硬化过程中细胞的特异性

摘要：

动脉粥样硬化是一种出现在动脉壁的慢性疾病，其特征是在内膜中脂肪和纤维物质的积聚。动脉粥样硬化是心血管疾病的主要原因，而后者与高死亡率和发病率有关，特别是在老龄人群中。细胞凋亡是一种受到严格调控的程序性细胞死亡形式，可清除不需要或有害的细胞。细胞凋亡在动脉粥样硬化中的作用一直是最近研究的热点。此次描述性综述全面阐述了细胞凋亡对动脉粥样硬化的影响。凋亡对动脉粥样硬化的影响主要取决于细胞类型和疾病分期。其中内皮细胞凋亡因衰老而加剧，可能会破坏血管内壁的完整性，从而促进脂质渗透到内皮下空间，进而促进斑块脆性。有证据表明，血管平滑肌细胞凋亡可在动脉粥样硬化早期抑制其迁移和增殖，减轻斑块形成，但在晚期也会通过使纤维帽变薄来诱导斑块不稳定。巨噬细胞凋亡也在动脉粥样硬化中起着双重作用，其也取决于时间，在早期抑制病变细胞数量并抑制斑块进展，在晚期则会加剧坏死核心发育和斑块脆性。尽管还需要更多的研究来充分阐明细胞凋亡在动脉粥样硬化中的作用，但其似乎是解决这种多因素疾病的一种潜在靶点。