The role of subfractions of high density lipoprotein in reverse cholesterol transport : the rabbit as an experimental model
Coronary heart disease (CHD) is a major cause of death and incapacitation. CHD may arise after decades of degenerative disease in the arteries, where cholesterol is deposited. The only alternative for the removal of cholesterol from the arteries, and therefore prevention of long-term lesions, is "reverse cholesterol transport" (RCT), a mechanism mediated by high density lipoprotein (HDL). The present thesis was concerned with the role of specific subfractions of HDL which are relevant to RCT. In this study, the rabbit was proven to be a very good model, with similar lipid and HDL profile to humans. With the aid of acute cholesterol loading into endothelial cells of the rabbits, and the study of alterations of the profile of subfractions of HDL, it may be concluded that there are two pathways for RCT in the rabbit: one involving only the very small and the very large HDL particles, which appears to be the acute response to cholesterol-loading; and another pathway, involving HDL particles of intermediate size as well, which appears to be a continuous response to cholesterol-loading. Different subfractions of HDL were also shown to contain different levels of tocopherols and carotenes, which are considered to have a protective role against CHD. Binding of specific subfractions of HDL to the liver, which would be an important step in RCT, has not shown the presence of a specific receptor for HDL subfractions. The measurement of plasma levels of specific subfractions of HDL, which are of particular relevance to RCT, both in clinical trials and epidemiological studies may be an important tool to disclose individuals at risk of CHD.