Possible Regulation of Platelets by Native and Modified Low Density Lipoprotein-Cholesterol Particles

An excess number of low density lipoprotein-cholesterol (LDL-C) particles is an independent risk for a cardiovascular event in the future. LDL particles diffused into the developing atherosclerotic plaques bind to proteoglycans in the intima, become oxidized and phagocytosed to macrophages. This causes the generation of foam cells, which aggravate the generation of fatty streaks and induce platelet attachment.1) It is highly probable that platelets may have contact with oxidiz-ed LDL (oxLDL).2)3) Several results describe that oxLDL can be expos-ed to circulating blood or can even be formed in plasma at sites of oxidative stress. Platelets express a series of receptors that specifi-cally recognize oxLDL, such as CD36 and scavenger receptor A (SRA). oxLDL-bound CD36 and SRA induce phosphorylation of p38 MAP kinase (MAPK), which in turn triggers the production of thrombox-ane A2 through the activation of a cytoplasmic type of phospholi-pase A2.4) Thus, the stimulation with oxLDL enables platelets to in-duce aggregation independently or with other stimulatory signals such as adenosine diphosphate (ADP), collagen or thrombin in a sy-nergistic manner. Unlike oxLDL, native and non-oxLDL particles are functionally inert and little has been described regarding the activity of native LDL on any type of cells that may contribute to the development of athero