Low-density lipoprotein oxidation, antioxidants and risk of atherosclerosis
1997
textabstractCardiovascular 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.
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