title: Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy.
abstract: Low-density lipoprotein (LDL)-cholesterol is important for cellular function, but in high concentrations, it can lead to atheroma formation. Over the past several decades, it has become abundantly evident that the oxidized form of LDL-cholesterol (ox-LDL) is more important in the genesis and progression of atherosclerosis than native unmodified LDL-cholesterol. Ox-LDL leads to endothelial dysfunction, an initial step in the formation of an atheroma. Ox-LDL acts via binding to a number of scavenger receptors (SR), such as SR-A1, SR-A2 and lectin-like oxidized low-density lipoprotein receptor (LOX-1). Ox-LDL can upregulate expression of its own receptor LOX-1 on endothelial cells and activate these cells. In addition, ox-LDL promotes the growth and migration of smooth muscle cells, monocytes/macrophages and fibroblasts. Ox-LDL also leads to the generation of reactive oxygen species that in physiologic concentrations combat invasion of the body by noxious agents, but when in excess, can lead to a state of oxidative stress. There is evidence for the presence of oxidative stress in a host of conditions such as atherosclerosis and aging. In this review, we discuss the role of oxidative stress, ox-LDL and LOX-1 in atherogenesis and the reasons why the traditional approaches to limit oxidant stress have not been successful.
authors: Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors: Sona
authors: S
authors: Mitra
authors: Abhishek
authors: A
authors: Deshmukh
authors: Rajesh
authors: R
authors: Sachdeva
authors: Jingjun
authors: J
authors: Lu
authors: Jawahar L
authors: JL
authors: Mehta
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051127:Scavenger Receptors, Class E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D000804:Angiotensin II