Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions

Initiation of atherosclerosis is characterized by accumulation of aggregate s of small lipid droplets and vesicles in the extracellular matrix: of the arterial intima, The droplets and vesicles have features that suggest that they are formed from modified plasma-derived low density lipoprotein (LDL) particles. A variety of hydrolytic enzymes and prooxidative agents that cou ld lead to extracellular assembly of LDL-derived droplets and vesicles are present in the arterial intima, In fact, in vitro studies have demonstrated that extensive oxidation of LDL and treatment of LDL with either proteolyt ic or Lipolytic enzymes will induce LDL aggregation and fusion and treatmen t of LDL with cholesterol esterase will cause formation of vesicles, Fusion of LDL particles proceeds faster in vitro when they are bound to component s of the extracellular matrix derived from the arterial intima, such as pro teoglycans, and, depending on the type of modification, the strength of bin ding of modified LDL to the matrix components may either increase or decrea se. In the present article, we discuss molecular mechanisms that provide cl ues as to how aggregated lipid droplets and vesicles may be derived from mo dified LDL particles. We also describe how these modified forms of LDL, by means of their trapping to the extracellular matrix, may lead to extracellu lar lipid accumulation in the arterial intima.