Low-density lipoprotein oxidation, antioxidants and risk of atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death in most industrialized countries. In the Netherlands, it is responsible for 40% of all deaths. Major risk factors for CVD are identified such as smoking, high cholesterol level and hypertension. Other important determinants of cardiovascular risk are nutrition, physical activity and body weight. However, these known risk factors cannot fully explain individual differences in cardiovascular risk. An intriguing hypothesis has been postulated in which the known beneficial effect of a diet high in flUit and vegetables is combined with the known harmful effect of high cholesterol levels or, more specifically, high low-density lipoprotein (LDL) cholesterol levels. This hypothesis describes a high level of LDL cholesterol as a promoting factor in atherosclerosis after LDL has been chemically altered by free radical compounds. The uptake of cholesterol in macrophages is increased and foam cells are formed. These foam cells can cluster just beneath the intima of the vessel wall which is the beginning of the fatty streak and of the atherogenic process. Antioxidants can playa role in protecting LDL from oxidation by scavenging free radicals. Several lines of evidence have indicated that oxidation occurs in vivo and that antioxidants may have a preventive effect. Epitopes of oxidized LDL are found in atherosclerotic lesions.Further, supplementation with vitamin E has been reported to decrease susceptibility of LDL to oxidation. Evidence for direct relations between susceptibility to oxidation and risk of cardiovascular diseases, however, is scarce. To investigate susceptibility of LDL to oxidation and the preventive role of antioxidants in relation to atherosclerosis, we performed the studies described in this thesis.