The effects of modified low density lipoprotein on coronary artery endothelial and smooth muscle cells

Elevated plasma levels of low density lipoprotein (LDL) are associated with an increased risk of atherosclerotic disease, and oxidative modification of LDL is believed to enhance its atherogenic potential. Modified LDL is thought to be involved in intimal fatty streak formation; the earliest detectable stage of atherosclerosis. The characteristic cells within the fatty streak are lipid laden macrophage foam cells. Foam cells are derived from circulating monocytes, which adhere to the vessel wall before migrating into the intima. This thesis is an in vitro investigation of the interactions between modified LDL and the cells of the human coronary artery wall: endothelial and smooth muscle cells, and of the role of modified LDL in the adhesion of monocytes to these cells. Described herein are: 1. The isolation, culture and chararcterisation of human endothelial cells from coronary artery and other vessels. 2. The isolation, culture and chararcterisation of human coronary artery and aortic smooth muscle cells. 3. The isolation and oxidative modification of human LDL of low pyrogenicity. 4. The effects of native and modified LDL on the basic cellular processes of endothelial and smooth muscle cells. 5. An investigation of the adhesion of human monocytes to endothelial and smooth muscle cells stimulated by native and modified LDL, and the role of adhesion molecules in this process