Monaco Claudia, McNamara Coleen A, Slütter Bram, Foks Amanda C, Bekiranov Stefan, Mulder Willem J M, Goncalves Isabel, Lutgens Esther
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
Carter Immunology Research Center, Division of Cardiology, University of Virginia, Charlottesville, Virginia, United States.
Physiol Rev. 2025 Oct 1;105(4):2141-2230. doi: 10.1152/physrev.00016.2024. Epub 2025 May 21.
Cardiovascular disease is the global number one cause of mortality and morbidity. The majority of cardiovascular diseases are caused by atherosclerosis, a lipid-driven, inflammatory disease of the middle- and large-sized arteries. The disease is characterized by the formation of atherosclerotic plaques throughout the arterial tree. Over the years, insights into the pathogenesis of atherosclerosis have shifted from a "lipid-driven" model to a "response-to-injury" perspective and more recently to a "lipid-driven inflammatory disease" viewpoint. We are now aware that a network of multiple immune cell types and subsets of the innate and adaptive immune system inhabit our arteries. Intricate interactions between these immune cell subsets, nonimmune cells, and local environmental substances such as lipids, cell debris, and calcium cause a fluidic balance of proinflammatory and regulatory responses. A dysregulation of this balance toward a proinflammatory milieu drives atherosclerotic disease progression. Although we have acknowledged that atherosclerosis is an inflammatory disease, state-of-the-art treatments are still based on lipid-lowering, antihypertensive, and lifestyle-changing strategies. In the past decade, clinical phase I, II, and III trials targeting the immune system revealed that patients tolerate immunotherapy, show decreased inflammation, and/or have a reduction in cardiovascular endpoints. However, the search for novel immunotherapeutic targets and treatment regimens as well as stratification of patients who would benefit from such treatments to combat atherosclerotic cardiovascular disease is only just beginning. In this review article, we will highlight the newest insights on the different cell subsets and components of the immune system in atherosclerosis and elaborate on current and future immunotherapeutics to treat atherosclerotic cardiovascular disease.
心血管疾病是全球首要的死亡和发病原因。大多数心血管疾病由动脉粥样硬化引起，这是一种由脂质驱动的中大型动脉炎症性疾病。该疾病的特征是在整个动脉树中形成动脉粥样硬化斑块。多年来，对动脉粥样硬化发病机制的认识已从“脂质驱动”模型转变为“损伤反应”观点，最近又转变为“脂质驱动的炎症性疾病”观点。我们现在知道，多种免疫细胞类型以及先天和适应性免疫系统的亚群网络存在于我们的动脉中。这些免疫细胞亚群、非免疫细胞与脂质、细胞碎片和钙等局部环境物质之间复杂的相互作用导致促炎反应和调节反应的流体平衡。这种平衡向促炎环境的失调会推动动脉粥样硬化疾病的进展。尽管我们已经认识到动脉粥样硬化是一种炎症性疾病，但目前的先进治疗方法仍然基于降脂、抗高血压和改变生活方式的策略。在过去十年中，针对免疫系统的临床I期、II期和III期试验表明，患者能够耐受免疫疗法，炎症减轻，和/或心血管终点有所降低。然而，寻找新的免疫治疗靶点和治疗方案，以及对将从这类治疗中受益的患者进行分层以对抗动脉粥样硬化性心血管疾病的工作才刚刚开始。在这篇综述文章中，我们将重点介绍关于动脉粥样硬化中免疫系统不同细胞亚群和组成部分的最新见解，并详细阐述治疗动脉粥样硬化性心血管疾病的当前和未来免疫疗法。
