Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY, 11501, USA.
Inflamm Res. 2020 Oct;69(10):975-988. doi: 10.1007/s00011-020-01382-6. Epub 2020 Jul 22.
Cardiovascular disease (CVD) is the leading cause of death, globally, and its prevalence is only expected to rise due to the increasing incidence of co-morbidities such as obesity and diabetes. Medical treatment of CVD is directed primarily at slowing or reversing the underlying atherosclerotic process by managing circulating lipids with an emphasis on control of low-density lipoprotein (LDL) cholesterol. However, over the past several decades, there has been increasing recognition that chronic inflammation and immune system activation are important contributors to atherosclerosis. This shift in focus has led to the elucidation of the complex interplay between cholesterol and cellular secretion of cytokines involved in CVD pathogenesis. Of the vast array of cytokine promoting atherosclerosis, interferon (IFN)-γ is highly implicated and, therefore, of great interest.
Literature review was performed to further understand the effect of IFN-γ on the development of atherosclerotic CVD.
IFN-γ, the sole member of the type II IFN family, is produced by T cells and macrophages, and has been found to induce production of other cytokines and to have multiple effects on all stages of atherogenesis. IFN-γ activates a variety of signaling pathways, most commonly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, to induce oxidative stress, promote foam cell accumulation, stimulate smooth muscle cell proliferation and migration into the arterial intima, enhance platelet-derived growth factor expression, and destabilize plaque. These are just a few of the contributions of IFN-γ to the initiation and progression of atherosclerotic CVD.
Given the pivotal role of IFN-γ in the advancement of CVD, activation of its signaling pathways is being explored as a driver of atherosclerosis. Manipulation of this key cytokine may lead to novel therapeutic avenues for CVD prevention and treatment. A number of therapies are being explored with IFN-γ as the potential target.
心血管疾病（CVD）是全球范围内的主要死亡原因，由于肥胖症和糖尿病等合并症的发病率不断上升，其患病率预计只会上升。CVD 的医疗治疗主要通过管理循环脂质来针对减缓或逆转潜在的动脉粥样硬化过程，重点是控制低密度脂蛋白（LDL）胆固醇。然而，在过去几十年中，人们越来越认识到慢性炎症和免疫系统激活是动脉粥样硬化的重要促成因素。这种重点的转变导致了阐明胆固醇与细胞分泌参与 CVD 发病机制的细胞因子之间的复杂相互作用。在促进动脉粥样硬化的大量细胞因子中，干扰素（IFN）-γ高度牵连，因此非常有趣。
进行文献综述，以进一步了解 IFN-γ对动脉粥样硬化性 CVD 发展的影响。
IFN-γ是 II 型 IFN 家族的唯一成员，由 T 细胞和巨噬细胞产生，已发现其诱导其他细胞因子的产生，并对动脉粥样硬化形成的所有阶段具有多种作用。IFN-γ激活多种信号通路，最常见的是 Janus 激酶（JAK）/信号转导和转录激活因子（STAT）通路，以诱导氧化应激，促进泡沫细胞积聚，刺激平滑肌细胞增殖和向动脉内膜迁移，增强血小板衍生生长因子的表达，并使斑块不稳定。这些只是 IFN-γ对动脉粥样硬化性 CVD 的起始和进展的一些贡献。
鉴于 IFN-γ在 CVD 进展中的关键作用，其信号通路的激活被探索为动脉粥样硬化的驱动因素。对这种关键细胞因子的操纵可能会为 CVD 的预防和治疗开辟新的治疗途径。正在探索许多疗法，IFN-γ是潜在的靶标。
