BIOACTIVE FOOD COMPONENTS AND MODULATION OF ATHEROSCLEROSIS AND ANGIOGENESIS
Location: Human Nutrition Research Center on Aging
Title: LDL oxidation as a biomarker of antioxidant status
| Meydani, Mohsen - |
| Kong, Eun Hee - |
| Knight, Ashley - |
Submitted to: Biomarkers for Antioxidant Defense and Oxidative Damage Principles and Practical Applications
Publication Type: Book / Chapter
Publication Acceptance Date: April 15, 2010
Publication Date: September 1, 2010
Citation: Meydani, M., Kong, E., Knight, A. 2010. LDL oxidation as a biomarker of antioxidant status. Biomarkers for Antioxidant Defense and Oxidative Damage Principles and Practical Applications. Malden, MA: Blackwell Publishing Ltd. p. 51-64.
During the past four decades, several hypotheses have evolved about the cause of atherosclerosis including vascular response to injury, vascular wall retention of low density lipoprotein (LDL), and oxidative modification of LDL. Because plasma contains robust antioxidant defenses and LDL contains lipid soluble antioxidant defenses, LDL oxidation mainly occurs in the vascular wall, and is less likely to occur in circulation. While LDL is well recognized as atherogenic, the severity of atherogenicity of LDL is dependent on the size of LDL particles, which vary in size and density. The presence of small, dense LDL particles (sdLDL) in circulation is considered to be a high risk factor for coronary heart disease (CHD).These particles are very susceptible to oxidative modification and their atherogenicity may be related to their small size so that they can penetrate through endothelium and sub-endothelial spaces in the arteries. According to the oxidative modification hypothesis of atherosclerosis, native LDL is not atherogenic; rather oxidatively modified LDL is the main cause and source of lipids that accumulate during atherogenesis. Oxidatively modified LDL attracts circulating monocytes into the intimal space, where they become resident monocytes-macrophages expressing scavenger receptors through which they internalize oxidized LDL, accumulate large amount of lipids, and become lipid-laden foam cells. However, if the LDL is severely oxidized, it is then termed “oxidized-LDL” (ox-LDL) and has higher electrophoretic mobility, higher density and higher free cholesterol content than native LDL. Ox-LDL attracts monocytes and T lymphocytes and it inhibits macrophage motility, so that they become resident macrophages in the sub-endothelial space accumulating lipids. It has been established that the higher the LDL cholesterol in the blood stream, the higher the levels of oxLDL in circulation. Thus, oxidized LDL is more atherogenic than native LDL and is readily recognized by the scavenger receptors on monocyte-derived macrophages. Further, elevated oxLDL in circulation is strongly associated with elevated LDL and triglyceride levels, as for example, in prediabetic patients. While each hypothesis points to its critical initiating event, all share common complex cellular events, which include several components of inflammation, such as monocytes, macrophages, T cells and inflammatory cytokines; therefore, atherosclerosis is now believed to be an inflammatory disease of arteries.