Department of Medical Biochemistry, Experimental Vascular Biology, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 15, 1105 CZ Amsterdam, The Netherlands.
Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian's University (LMU), Pettenkoferstraße 8a, 80336 Munich, Germany.
Cardiovasc Res. 2018 Mar 1;114(3):368-377. doi: 10.1093/cvr/cvx248.
In the past decades, the inflammatory nature of atherosclerosis has been well-recognized and despite the development of therapeutic strategies targeted at its classical risk factors such as dyslipidemia and hypertension, atherosclerosis remains a major cause of morbidity and mortality. Additional strategies targeting the chronic inflammatory pathways underlying the development of atherosclerosis are therefore required. Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis. Immune checkpoint proteins have a critical role in facilitating immune cell interactions and play an essential role in the development of atherosclerosis. Although the therapeutic potential of these molecules is well-recognized in clinical oncology, the use of immune checkpoint modulators in atherosclerosis is still limited to experimental models. Here, we review recent insights on the role of immune checkpoint proteins in atherosclerosis. Additionally, we explore the therapeutic potential and challenges of immune checkpoint modulating strategies in cardiovascular medicine and we discuss novel therapeutic approaches to target these proteins in atherosclerosis.
在过去的几十年中，动脉粥样硬化的炎症性质已得到充分认识，尽管针对其经典危险因素（如血脂异常和高血压）制定了治疗策略，但动脉粥样硬化仍然是发病率和死亡率的主要原因。因此，需要针对动脉粥样硬化发展背后的慢性炎症途径制定其他策略。不同免疫细胞之间的相互作用会导致炎症介质（例如细胞因子和趋化因子）的分泌，并促进动脉粥样硬化的发生。免疫检查点蛋白在促进免疫细胞相互作用方面起着至关重要的作用，并在动脉粥样硬化的发生发展中起着重要作用。尽管这些分子的治疗潜力在临床肿瘤学中得到了充分认可，但免疫检查点调节剂在动脉粥样硬化中的应用仍仅限于实验模型。在这里，我们回顾了免疫检查点蛋白在动脉粥样硬化中的作用的最新见解。此外，我们探讨了免疫检查点调节策略在心血管医学中的治疗潜力和挑战，并讨论了针对这些蛋白质在动脉粥样硬化中治疗的新方法。
