LipoLab, Yeungnam University, Gyeongsan 38541, Korea.
Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Korea.
Int J Mol Sci. 2022 Apr 2;23(7):3967. doi: 10.3390/ijms23073967.
The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one's lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer's disease and Parkinson's disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one's lifetime.
高密度脂蛋白（HDL）的数量表示为血清 HDL-C 浓度（mg/dL），而 HDL 的质量表现为蛋白质和脂质含量、氧化程度和糖化程度的不同特征。HDL 的功能代表了 HDL 的几个性能指标，如抗氧化、抗炎和胆固醇外排活性。HDL 的数量和质量可以在一个人的一生的不同阶段发生变化，这取决于感染、疾病和生活方式，如饮食习惯、运动和吸烟。HDL 的数量可以根据年龄和性别而变化，例如青春期、中年症状、更年期和绝经期。在疾病状态下，HDL-C 会降低，如急性感染、慢性炎症和自身免疫性疾病，而通过定期的有氧运动和健康的食物摄入可以增加 HDL-C。一般来说，正常水平的高 HDL-C 与良好的 HDL 质量和功能有关。然而，高 HDL 数量并不总是伴随着良好的 HDL 质量或功能。HDL 的质量与 HDL 的形态有关，如颗粒大小、形状和数量。HDL 的质量还取决于 HDL 的组成，如载脂蛋白（ApoA-I、ApoA-II、ApoC-III、血清淀粉样蛋白 A 和α-突触核蛋白）、胆固醇和甘油三酯。HDL 的质量还与 HDL 修饰的程度有关，如糖化和氧化，导致 ApoA-I 的多聚化，以及聚集导致淀粉样变性。HDL 的质量通常决定了 HDL 的功能，这取决于附着的抗氧化酶活性，如对氧磷酶和胆固醇外排活性。传统的 HDL 功能是回归，即从动脉粥样硬化病变中去除胆固醇，以及从低密度脂蛋白（LDL）中去除氧化物质。最近，据报道，HDL 功能可以通过去除β-淀粉样斑块和抑制大脑中的α-突触核蛋白聚集来分别减轻阿尔茨海默病和帕金森病，从而扩展。最近，HDL 功能与 2019 年冠状病毒病（COVID-19）的易感性和恢复能力有关，通过抑制严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的活性。功能失调的 HDL 通常与许多急性传染病和慢性衰老相关疾病有关。HDL 可以作为一种合适的生物标志物，通过监测其数量和质量在抗氧化和抗炎能力方面的变化来诊断许多疾病及其进展。HDL 可以作为一种蛋白质药物，用于去除斑块，并作为非可溶性药物和基因的传递载体。功能失调的 HDL 具有较差的 HDL 质量，例如较低的 ApoA-I 含量、较低的抗氧化能力、较小的粒径和模糊的形状。本综述分析了 HDL 数量、质量和功能在一个人的一生的健康和疾病状态下的最新进展。
