Lipid peroxidation and its relation to Atherosclerosis
Loeckie et. al., (1999), had suggested that the small, dense oxidized low-density lipoproteins (oxLDL) are the most atherogenic particles. However, the increase in the small, dense LDLs is due to the increase in the level of triglycerides in human plasma. Lipid peroxidation is a form of oxidative tissue damage that occurs in polyunsaturated fatty acids (Gate et. al.,. 1999). The process is initiated by a hydroxyl radical (OH·) that captures a hydrogen atom from a polyunsaturated fatty acid (LH) in the phospholipids of membranes and produces lipid carbon-centered radical (R·). Lipid carbon-centered radicals (R·) rapidly react with molecular oxygen (O2) to generate a lipid peroxyl radical (ROO·). The peroxyl radical product is similarly highly reactive and can combine with other peroxyl radicals to alter membrane proteins. The lipid peroxyl radicals (ROO·) can also capture a hydrogen atom from the adjacent fatty acids (LH) to generate a chain reaction that propagates additional lipid carbon-centered radicals (R·) as well as generating lipid peroxides (ROOH) ( Groff and Gropper 2000; Gate et. al., 1999).
During lipid peroxidation, malondialdehyde (MDA), a highly reactive dialdehyde, can also be generated (Gate et. al., 1999). The process is initiated when a hydroxyl radical captures a hydrogen atom from a methylene carbon of the fatty acid. The process of lipid peroxidation can also occur upon exposure to hydrogen peroxide and superoxide radicals. Resulting structural alterations the cellular membranes bring about the release of cell and organelle contents, the loss of essential fatty acids, and the formation of cytosolic aldehyde and peroxide products (Burton et. al., 1990; Comporti, 1985).
Lipid peroxidation was measured by the MDA equivalent, using a fluorescence method of 2-thiobarbituric acid reactive substances (TBARS). (Mohammed and Guadalupe,1997). Lipid hydroperoxides, lipid hydroxides, hydrocarbons, and aldehydes are the stable degradation products of the lipid peroxidation.
The initial abstraction of a hydrogen atom in lipid peroxidation process can occur at different points on the carbon chain of the fatty acid. Thus, peroxidation of arachidonic acid for example gives six different lipid hydroperoxides. (Halliwell and Gutteridge, 1999). The number of double bonds determines the susceptibility of a fatty acid to peroxidation. Polyunsaturated fatty acids are readily attacked by free radicals, whereas saturated fatty acids with no double bond and monounsaturated fatty acids with one double bond are more resistant to peroxidation. An adjacent double bond weakens the energy of attachment of the hydrogen atoms present on the next carbon atom. Therefore, the greater the number of double bonds in a fatty acid chains, the easier the removal of a hydrogen atom. Therefore, PUFAs are more susceptible to lipid peroxidation. (Porter et. al., 1995; Wagner et. al.,1994).
Atherosclerosis is a variable combination of changes of the intima of arteries, consisting of the focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue and calcium deposits and associated with medial changes. (WHO,1958). Atherosclerosis develops through building up of plaque on the inside walls of arteries. Plaque is made up of low density lipoprotein (LDL), macrophages, smooth muscle cells, platelets, and other substances. It may narrow the lumen of a blood vessel and restrict blood flow. Plaque rupture can induce the formation of thrombus (blood clot) and block blood flow. This will result in ischemic stroke or heart attack.
In men and women, it has been suggested that antioxidant supplementation decreases the progression of atherosclerosis and that the high intake of vitamin E (an antioxidant) lowers the risk of coronary heart disease in both women and men. It has been reported that the sex difference in cardiovascular diseases may be partially attributable to modulation of lipoprotein metabolism by estrogens and their antioxidant effect. (Mohammed El Hafidi & Guadalupe Baños, 1997)
Written by Ting Ting on May 31st, 2006 with
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