Cardiovascular disease is the leading cause of death worldwide, and it commonly results from atherosclerotic plaque progression. One of the increasingly recognized drivers of atherosclerosis is dysfunctional efferocytosis, a homeostatic mechanism responsible for the clearance of dead cells and the resolution of inflammation. In atherosclerosis, the capacity of phagocytes to participate in efferocytosis is hampered, leading to the accumulation of apoptotic and necrotic tissue within the plaque, which results in enlargement of the necrotic core, increased luminal stenosis and plaque inflammation, and predisposition to plaque rupture or erosion. In this Review, we describe the different forms of programmed cell death that can occur in the atherosclerotic plaque and highlight the efferocytic machinery that is normally implicated in cardiovascular physiology. We then discuss the mechanisms by which efferocytosis fails in atherosclerosis and other cardiovascular and cardiometabolic diseases, including myocardial infarction and diabetes mellitus, and discuss therapeutic approaches that might reverse this pathological process.

心血管疾病是全世界死亡的主要原因，通常由动脉粥样硬化斑块进展引起。动脉粥样硬化的日益公认的驱动因素之一是功能失调的胞吐作用，这是一种负责清除死细胞和消退炎症的稳态机制。在动脉粥样硬化中，吞噬细胞参与胞吐作用的能力受到阻碍，导致斑块内凋亡和坏死组织积累，从而导致坏死核心扩大，管腔狭窄和斑块炎症增加，以及斑块破裂或糜烂的易感性。在这篇综述中，我们描述了动脉粥样硬化斑块中可能发生的不同形式的程序性细胞死亡，并强调了通常与心血管生理学有关的泡细胞机制。然后，我们讨论了动脉粥样硬化和其他心血管和心脏代谢疾病（包括心肌梗塞和糖尿病）中胞吐作用失败的机制，并讨论了可能逆转这一病理过程的治疗方法。