Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Curr Opin Lipidol. 2019 Oct;30(5):395-400. doi: 10.1097/MOL.0000000000000628.
The two major challenges in cardiovascular medicine are to refine risk prediction and to improve pharmacological prevention and treatment. The concept of innate immune memory, which is called trained immunity, has the potential to improve clinical practice in these regards.
Monocytes and macrophages have the capability to develop a long-term proinflammatory and proatherogenic phenotype after brief exposure to inflammatory stimuli, such as oxidized low-density lipoprotein particles. This innate immune memory develops because of rewiring of intracellular metabolic pathways and epigenetic reprogramming of histone modifications. The persistence of circulating hyperresponsive monocytes in vivo is explained by the fact that training occurs in myeloid progenitor cells in the bone marrow. Several recent studies reported the presence of monocytes with a trained immune phenotype in patients with established atherosclerosis, and in patients with an increased risk for atherosclerosis because of dyslipoproteinemia.
In monocytes and their bone marrow progenitors, metabolic and epigenetic reprogramming can induce trained immunity, which might contribute to the persistent nonresolving inflammation that characterizes atherosclerosis. These pathways offer exciting novel drug targets to improve the prevention and treatment of cardiovascular disease.
心血管医学的两大挑战是完善风险预测和改善药理学预防及治疗。先天免疫记忆的概念，即训练有素的免疫，有可能在这两方面改善临床实践。
单核细胞和巨噬细胞在短暂暴露于炎症刺激物（如氧化低密度脂蛋白颗粒）后，有能力发展出长期的促炎和动脉粥样硬化表型。这种先天免疫记忆的形成是由于细胞内代谢途径的重布线和组蛋白修饰的表观遗传重编程。循环中高反应性单核细胞在体内的持续存在可以用这样一个事实来解释，即训练发生在骨髓中的髓系祖细胞中。最近的几项研究报告称，在已患有动脉粥样硬化的患者以及由于脂蛋白异常血症而存在动脉粥样硬化风险增加的患者中，存在具有训练有素的免疫表型的单核细胞。
在单核细胞及其骨髓祖细胞中，代谢和表观遗传重编程可以诱导训练有素的免疫，这可能有助于持续存在的非解决炎症，这种炎症是动脉粥样硬化的特征。这些途径为改善心血管疾病的预防和治疗提供了令人兴奋的新药物靶点。
