New pieces in the puzzle of atherogenesis

The contributions of high serum levels of cholesterol to atherogenests has been widely recognized, but the mechanisms are not native low-density lipop roteins, are the particles incorporated into the arterial wall. A group of receptors generically called "scavenger" (SR), actively bing these modified lipoproteins and incorporate them into monocytes-macrophages, in the arter ial intima. SR are not down regulated by intracellular concentrations of ch olesterol, thus accumulating huge amounts of lipids, transforming monocyte- macrophages into foam cells, predominant cell type of the fatty streak. The simultaneous cytokine production and migration of other cellular types pro gressively transform this initial lesion into the organized atherosclerotic plaque. In this setting SR, which are up-regulated by oxidized LDL, play a central promoting role. Its presence has been demonstrated in arterial pla ques both in human and animal models, and its blockade protects animals fro m development or progression of atherosclerosis. In humans, elevated antibo dy titers to oxidized LDL in pattents with coronary stenosis, and increased SR activity, in pro-atherogenic conditions such as haemodyalists, definiti vely conclude that the oxidized-LDL-SR hypothesis is a finished puzzle.