Brunham Liam R
Centre for Heart Lung Innovation, Department of Medicine, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
J Lipid Res. 2025 Jan;66(1):100728. doi: 10.1016/j.jlr.2024.100728. Epub 2024 Dec 12.
High density lipoproteins (HDLs) are best known for their role in atherosclerotic cardiovascular diseases. However, efforts to reduce cardiovascular risk by increasing the concentration of cholesterol in HDL have failed, raising the question of whether HDL may have other, more central aspects to its role in health and disease. In epidemiological studies, low levels of HDL cholesterol are strongly associated with risk of infectious diseases and death from sepsis and, during sepsis, a larger decline in HDL cholesterol predicts a worse outcome. Many preclinical studies have examined strategies to augment HDL genetically or pharmacologically and have shown that this leads to protection from sepsis in animal models. Data in humans are more limited, but suggest a clinically relevant role of HDL in mediating the response to pathogen-associated lipids and preventing excessive inflammation. Collectively, these data raise the intriguing possibility that a clinically important biological function of HDL is as a component of the innate immune system and suggest that pharmacological manipulation of HDL may be a strategy to reduce the organ dysfunction and death that results from uncontrolled inflammation during sepsis. This review article discusses recent advances in our understanding of the role of HDL in sepsis.
高密度脂蛋白（HDL）因其在动脉粥样硬化性心血管疾病中的作用而最为人所知。然而，通过提高HDL中胆固醇浓度来降低心血管风险的努力却失败了，这就引发了一个问题，即HDL在健康和疾病中的作用是否可能还有其他更核心的方面。在流行病学研究中，HDL胆固醇水平低与感染性疾病风险以及败血症死亡密切相关，并且在败血症期间，HDL胆固醇水平的更大幅度下降预示着预后更差。许多临床前研究已经探讨了通过基因或药理学手段增强HDL的策略，并表明这能在动物模型中对败血症起到保护作用。人类方面的数据较为有限，但表明HDL在介导对病原体相关脂质的反应以及预防过度炎症方面具有临床相关作用。总体而言，这些数据提出了一个有趣的可能性，即HDL的一项重要临床生物学功能是作为先天免疫系统的一个组成部分，并表明对HDL进行药理学调控可能是一种策略，以减少败血症期间因不受控制的炎症导致的器官功能障碍和死亡。这篇综述文章讨论了我们对HDL在败血症中作用的理解的最新进展。
