The role of LDL is to transport cholesterol throughout the body, but high levels of LDL in the blood have been associated with an increased risk for atherosclerosis. In normal LDL, the cholesteryl ester core is in a liquid state at physiological temperatures due to the random ordering of the cholesteryl esters within the core. But, diets high in saturated fat can alter the cholesteryl ester core causing it t become more ordered leading to a liquid-crystalline state under physiological conditions, It has bee shown that this liquid crystalline state is more atherogenic. Preliminary studies using cryo-electron microscopy have further suggested that a liquid crystalline core may cause LDL to change from a spherical to discoid shape. This study intends to determine how the lipid composition of the core affects the shape and atherogenicity of LDL. To determine if the lipid composition of the LDL core can induce a shape change from spherical to discoid, three types of LDL will be developed with different lipid compositions. The shapes of these different LDL particles will be studied at different temperatures using cryo-electron microscopy. To determine how a shape change affects the atherogenicity of LDL, the binding affinity of LDL for LDL receptors and proteoglycans in the arterial wall will be studied. This study could show how diets high in saturated fat can induce a shape chang in LDL causing LDL to be more atherogenic therefore increasing the risk for atherosclerosis.
| Coronado-Gray, Andrea; van Antwerpen, Rik (2005) Lipid composition influences the shape of human low density lipoprotein in vitreous ice. Lipids 40:495-500 |
| Coronado-Gray, Andrea; van Antwerpen, Rik (2003) The physical state of the LDL core influences the conformation of apolipoprotein B-100 on the lipoprotein surface. FEBS Lett 533:21-4 |
