Atherosclerosis and effects of vitamin E
...rious purposes. But people who eat a diet containing high cholesterol and saturated fat, have a high blood LDL concentration, due to the fact that their liver have low number of LDL receptors. Fewer LDL receptors means liver is less able to remove the LDLs from the blood, creating more availability of LDLs to enter into the endothelial cells of the arteries. As mentioned earlier these LDLs can get oxidized and progress to the pathogenesis of atherosclerosis. The development of fatty streaks is due to the transport of LDL into the artery wall, a concentration dependent process that does not require receptor mediated endocytosis as in the cells. There will be high increase in the rate of LDL trapping in hypercholesterolemia and hypertensive conditions. The vascular endothelium is made up of a monolayer of endothelial cells. Although it functions as a barrier for nutrient transport, the endothelium is also involved pathophysiologic processes such as inflammation, thrombosis formation, control of vasomotor tone and cancer cell metastasis. The oxidation of LDL can occur in the microenvironment of the subendothelial space. Macrophages, endothelial and smooth muscle cells can oxidize LDLs in such a way that LDLs get oxidized when they come in contact with free radicals, the unstable, charged molecules found in the blood that are blamed for damaging tissue and genes. Free radicals are the molecules which contain an unpaired electron in its orbital. These are highly reactive in the body, oxidizing atoms and molecules, and the resulting oxidized particles are bioactive. They can induce endothelial expression and secretion of cytokines, growth factors and several cell surface adhesion molecules that are capable of recruiting circulating monocytes and T lymphocytes into the intima. Oxidized LDL activates the development of monocytes into macrophages, where the uptakes of oxidized LDLs by the scavenger receptors are rapid. It also inhibits the production of nitric oxide and prostacyclin, the two antithrombotic and vasodilating molecules released by the endothelium. Increased adherence of monocytes to the endothelium constitutes one of the early visible changes in atherosclerosis. Exposure of oxidized LDL to endothelial cells stimulates the expression of endothelium derived adhesion molecules. These molecules promote monocyte adhesion and subsequent migration into the intima where monocytes differentiate into macrophages. However, various researches indicate that vitamin E inhibits the oxidative modification of LDL and also may inhibit atherogenesis through several other mechanisms at the molecular and cellular levels. Vitamin E, one of the most important lipid-soluble antioxidant nutrients, is found in nut oils, sunflower seeds, whole grains, wheat germ, and spinach. It is mainly tocopherol and it is the major fat-soluble antioxidant present in the LDL particle. Alpha tocopherol is the most active form of vitamin E and the predominant lipophilic antioxidant for LDLs. On average, 5 to 9 vitamin E molecules are carried by each LDL particle and are believed to protect LDLs from oxidative damage. Studies have indicated that increasing the vitamin E content of LDL particles, increases LDL’s resistance to oxidation and decreases their uptake by macrophages. Vitamin E supplementation has also been reported to suppress macrophage uptake of oxidized LDLs in human arterial lesions. Likewise, other beneficial effects of vitamin associated with the LDLs are, thrombin, a serine protease that is involved in clot formation, could be generated by circulating lipoproteins. It was reported that...