Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany.
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany; Walther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany.
Pharmacol Ther. 2019 Jan;193:50-62. doi: 10.1016/j.pharmthera.2018.08.012. Epub 2018 Aug 25.
Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated as lipid particles accumulate and become trapped in vessel walls. The subsequent immune response, involving both adaptive and immune cells, progresses plaque development, which may be exacerbated under dyslipidemic conditions. Broad evidence, especially from animal models, clearly demonstrates the effect of lipids on immune cells from their development in the bone marrow to their phenotypic switching in circulation. Interestingly, recent research has also shown a long-lasting epigenetic signature from lipids on immune cells. Traditionally, cardiovascular therapies have approached atherosclerosis through lipid-lowering medications because, until recently, anti-inflammatory therapies have been largely unsuccessful in clinical trials. However, the recent Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) provided pivotal support of the inflammatory hypothesis of atherosclerosis in man spurring on anti-inflammatory strategies to treat atherosclerosis. In this review, we describe the interactions between lipids and immune cells along with their specific outcomes as well as discuss their future perspective as potential cardiovascular targets.
心血管疾病（CVD）仍然是全球范围内的主要死亡原因，动脉粥样硬化是主要的潜在病理学基础。脂质和免疫细胞之间的相互作用被认为是动脉粥样硬化发生过程中动脉壁慢性炎症的主要驱动力。动脉粥样硬化始于脂质颗粒的积累并被困在血管壁中。随后的免疫反应，包括适应性免疫细胞和固有免疫细胞，都会促进斑块的发展，而在血脂异常的情况下，这种发展可能会加剧。广泛的证据，特别是来自动物模型的证据，清楚地表明了脂质对骨髓中免疫细胞发育到循环中表型转换的影响。有趣的是，最近的研究还表明，脂质对免疫细胞有持久的表观遗传特征。传统上，心血管疗法通过降低血脂的药物来治疗动脉粥样硬化，因为直到最近，抗炎疗法在临床试验中基本上都没有成功。然而，最近的 Canakinumab Antiinflammatory Thrombosis Outcomes Study（CANTOS）为动脉粥样硬化的炎症假说提供了重要的支持，这促使人们采用抗炎策略来治疗动脉粥样硬化。在这篇综述中，我们描述了脂质和免疫细胞之间的相互作用及其特定的作用，同时还讨论了它们作为潜在心血管靶点的未来前景。
