Psychosocial stress' effects on macrophage dynamics in atherosclerosis

总结 动脉粥样硬化是心肌梗死和中风的根本原因， 以脂蛋白和白细胞积聚为特征的慢性炎性疾病 血管壁在白细胞中，单核细胞衍生的内膜巨噬细胞可以说是最多的 决定性因素的发展，进展，恶化，和退化 动脉粥样硬化作为炎症、蛋白水解、氧化应激、脂质清除的关键效应物， 和巨噬细胞增多症，巨噬细胞一直是治疗 动脉粥样硬化然而，血管壁中的巨噬细胞含量是高度动态的，依赖于 由不同的生物学途径控制的多个系统和局部过程。 最近，我们发现，心理社会压力，这可能会导致心血管疾病（CVD）， 通过干扰巨噬细胞供应链来加剧动脉粥样硬化;动物受到 间歇性的心理社会压力发展成炎症性病变， 巨噬细胞。在这个项目中，我们将探讨压力如何影响与以下相关的机制： 单核细胞的流入（骨髓生成，单核细胞和干细胞的动员， 髓外骨髓生成和单核细胞流入病变），病变中巨噬细胞积聚 （巨噬细胞分化和局部增殖）和巨噬细胞流出（巨噬细胞死亡 通过凋亡、坏死或继发性坏死和巨噬细胞移出）。总的来说， 我们称之为巨噬细胞动力学。我们将研究压力对 动脉粥样硬化进展和消退中的巨噬细胞动力学，特别关注 交感神经系统和神经元引导信号的影响。我们将确认 控制与巨噬细胞动力学相关的过程的节点，其最终目的是靶向 他们治疗。

SUMMARY Atherosclerosis, the underlying cause of myocardial infarction and stroke, is a lipid-driven chronic inflammatory disease characterized by lipoprotein and leukocyte accumulation in the vessel wall. Among leukocytes, monocyte-derived intimal macrophages are arguably the most decisive contributors to the development, progression, exacerbation, and regression of atherosclerosis. As key effectors of inflammation, proteolysis, oxidative stress, lipid clearance, and efferocytosis, macrophages have long been therapeutic targets for the treatment of atherosclerosis. However, macrophage content in the vessel wall is highly dynamic, relying on multiple systemic and local processes that are governed by distinct biological pathways. Recently, we showed that psychosocial stress, which potentiates cardiovascular disease (CVD), aggravates atherosclerosis by disturbing the macrophage supply chain; animals subjected to intermittent psychosocial stress developed inflamed lesions containing more numerous macrophages than controls. In this project, we will ask how stress affects mechanisms related to influx of monocytes (medullary myelopoiesis, mobilization of monocytes and stem cells, extramedullary myelopoiesis, and monocyte influx to lesions), macrophage accrual in lesions (macrophage differentiation and local proliferation), and macrophage efflux (macrophage death through apoptosis, necrosis, or secondary necrosis, and macrophage emigration). Collectively, we refer to these as macrophage dynamics. We will investigate the impact of stress on macrophage dynamics in the progression and regression of atherosclerosis, with specific focus on the sympathetic nervous system and neuronal guidance cues. We will identify the decision nodes that control processes related to macrophage dynamics with the ultimate aim of targeting them therapeutically.