Electronegative LDL: An Active Player in Atherogenesis or a By-Product of Atherosclerosis?

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.