Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain.
Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
Curr Med Chem. 2019;26(9):1665-1679. doi: 10.2174/0929867325666180330093953.
Low-density lipoproteins (LDLs) are the major plasma carriers of cholesterol. However, LDL particles must undergo various molecular modifications to promote the development of atherosclerotic lesions. Modified LDL can be generated by different mechanisms, but as a common trait, show an increased electronegative charge of the LDL particle. A subfraction of LDL with increased electronegative charge (LDL(-)), which can be isolated from blood, exhibits several pro-atherogenic characteristics. LDL(-) is heterogeneous, due to its multiple origins but is strongly related to the development of atherosclerosis. Nevertheless, the implication of LDL(-) in a broad array of pathologic conditions is complex and in some cases anti-atherogenic LDL(-) properties have been reported. In fact, several molecular modifications generating LDL(-) have been widely studied, but it remains unknown as to whether these different mechanisms are specific or common to different pathological disorders. In this review, we attempt to address these issues examining the most recent findings on the biology of LDL(-) and discussing the relationship between this LDL subfraction and the development of different diseases with increased cardiovascular risk. Finally, the review highlights the importance of minor apolipoproteins associated with LDL(-) which would play a crucial role in the different properties displayed by these modified LDL particles.
低密度脂蛋白（LDLs）是胆固醇的主要血浆载体。然而，LDL 颗粒必须经历各种分子修饰才能促进动脉粥样硬化病变的发展。修饰的 LDL 可以通过不同的机制产生，但作为一个共同的特征，显示 LDL 颗粒的负电性增加。LDL（LDL（-））的一个亚组分，其带电量增加，可以从血液中分离出来，表现出几种促动脉粥样硬化的特征。LDL（-）是异质的，由于其多种来源，但与动脉粥样硬化的发展密切相关。然而，LDL（-）在广泛的病理条件下的影响是复杂的，在某些情况下，已经报道了抗动脉粥样硬化的 LDL（-）特性。事实上，已经广泛研究了产生 LDL（-）的几种分子修饰，但尚不清楚这些不同的机制是否是特定的，还是与不同的病理紊乱共同的。在这篇综述中，我们试图通过检查 LDL（-）生物学的最新发现来解决这些问题，并讨论这种 LDL 亚组分与增加心血管风险的不同疾病的发展之间的关系。最后，综述强调了与 LDL（-）相关的小载脂蛋白的重要性，它们在这些修饰的 LDL 颗粒显示的不同特性中发挥着关键作用。
