Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Department of Cardiology, 101 Hospital of PLA, Wuxi, Jiangsu province 214041, China.
Int J Med Sci. 2018 Oct 20;15(13):1555-1563. doi: 10.7150/ijms.27238. eCollection 2018.
Atherosclerosis is one kind of chronic inflammatory disease, in which multiple types of immune cells or factors are involved. Data from experimental and clinical studies on atherosclerosis have confirmed the key roles of immune cells and inflammation in such process. The thymus as a key organ in T lymphocyte ontogenesis has an important role in optimizing immune system function throughout the life, and dysfunction of thymus has been proved to be associated with severity of atherosclerosis. Based on previous research, we begin with the hypothesis that low density lipoprotein or cholesterol reduces the expression of the thymus transcription factor Foxn1 via low density lipoprotein receptors on the membrane surface and low density lipoprotein receptor related proteins on the cell surface, which cause the thymus function decline or degradation. The imbalance of T cell subgroups and the decrease of naive T cells due to thymus dysfunction cause the increase or decrease in the secretion of various inflammatory factors, which in turn aggravates or inhibits atherosclerosis progression and cardiovascular events. Hence, thymus may be the pivotal role in coronary heart disease mediated by atherosclerosis and cardiovascular events and it can imply a novel treatment strategy for the clinical management of patients with atherosclerosis in addition to different commercial drugs. Modulation of immune system by inducing thymus function may be a therapeutic approach for the prevention of atherosclerosis. Purpose of this review is to summarize and discuss the recent advances about the impact of thymus function on atherosclerosis by the data from animal or human studies and the potential mechanisms.
动脉粥样硬化是一种慢性炎症性疾病,涉及多种类型的免疫细胞或因子。来自动脉粥样硬化的实验和临床研究的数据证实了免疫细胞和炎症在这一过程中的关键作用。胸腺作为 T 淋巴细胞发生的关键器官,在整个生命周期中对优化免疫系统功能具有重要作用,并且已经证明胸腺功能障碍与动脉粥样硬化的严重程度有关。基于先前的研究,我们从假设开始,即低密度脂蛋白或胆固醇通过细胞膜表面的低密度脂蛋白受体和细胞表面的低密度脂蛋白受体相关蛋白降低胸腺转录因子 Foxn1 的表达,导致胸腺功能下降或退化。由于胸腺功能障碍导致 T 细胞亚群失衡和幼稚 T 细胞减少,导致各种炎症因子的分泌增加或减少,进而加重或抑制动脉粥样硬化进展和心血管事件。因此,胸腺可能是动脉粥样硬化和心血管事件介导的冠心病的关键作用,并为除了不同商业药物之外的动脉粥样硬化患者的临床管理提供了新的治疗策略。通过诱导胸腺功能来调节免疫系统可能是预防动脉粥样硬化的一种治疗方法。本综述的目的是总结和讨论来自动物或人类研究的数据中,关于胸腺功能对动脉粥样硬化影响的最新进展及其潜在机制。