Beyond oxidized LDL: the initiation and progression of atherosclerosis

Oxidized-low density lipoprotein (ox-LDL) exhibits various atherogenic properties, such as the formation of foam cells, the recruitment of macrophages into arteries, the promotion of cell growth, the formation of thrombi, and the development of vasoconstriction. Antioxidants inhibit atherosclerosis in cholesterol-fed animals by preventing the recruitment of macrophages into the arteries suggesting that oxidation is important for such recruitment of macrophages, and that it is responsible for early development of atherosclerosis. Calcification and an increase in extracellular matrix (ECM) are frequently observed in advanced atherosclerosis. These processes are active and regulated, not passive and degenerative, and do not appear to be controlled by ox-LDL. The control of calcifications and ECM increase will provide new directions in the treatment of atherosclerosis especially in the advanced stages. Future treatment should include strategies to inhibit the calcification and the increase in ECM.