Reactive oxygen species and death: oxidative DNA damage in atherosclerosis.

Oxidative Modification of LDL Although LDL is essential to deliver cholesterol to tissues, increased LDL cholesterol is associated with increased risk of cardiovascular disease. Oxidative modification of LDL promotes recruitment and retention of monocytes3 with formation of fatty streaks, the earliest lesions in atherosclerosis.4 Both macrophages and vascular smooth muscle cells (VSMCs) bind oxidized LDL via specific scavenger receptors,5,6 forming foam cells. Macrophage foam cells contain potent oxidant-generating systems that target lipids, including myeloperoxidase, nitric oxide (NO) synthase, and 15-lipoxygenase, allowing increased recognition and uptake by macrophages, creating a positive feedback loop.