Low-density lipoprotein (LDL) is a plasma lipoprotein particle whose lipid component includes cholesterol and triglycerides and is commonly referred to as 揵ad cholesterol?due to its role promoting atherogenic heart disease. LDL in the plasma originates from very-low density lipoprotein (vLDL) produced by the liver with the apoprotein B-100. vLDL is converted to LDL by the action of lipoprotein lipase, an enzyme that hydrolyzes triglycerides in vLDL, removing them from the vLDL particle and releasing free fatty acids. The removal of triglycerides from vLDL by lipoprotein lipase leaves a greater proportion of cholesterol, increasing the density of the particle and changing it to LDL.
Atherogenic heart disease involves the formation of plaques in arterial walls that narrow the arterial passage, restricting blood flow and increasing the risk of occlusion of blood flow by a myocardial infarction. One of the first steps in the development of atherogenic heart disease is the passage of LDL out of the arterial lumen and into the arterial wall. Once there, the lipids in LDL are chemically modified and oxidized. Oxidized LDL stimulates inflammatory signaling by neighboring endothelial cells, releasing chemokines and cytokines such as M-CSF and MCP-1 and recruiting monocytes into the arterial wall. Once there, monocytes differentiate into macrophages and internalize modified LDL. These macrophages continue to internalize LDL, becoming enlarged and full of lipid. These cells accumulate in tissue and are transformed into foam cells, dying and forming part of the atherogenic plaque.
Therapeutic intervention in atherogenic heart disease focuses first on lowering plasma LDL levels through diet and medication. The statins are drugs commonly used to block cholesterol production and increase the expression of the LDL receptor by the liver, removing LDL from circulation. Blocking LDL oxidation may also protect against atherogenesis, and may be the mechanism by which antioxidants such as vitamin E are proposed to reduce heart disease. Blocking the uptake of LDL by macrophages or inhibiting the inflammatory reaction against modified LDL may also offer routes to reduce the formation of atherogenic plaques.
