Atherosclerosis and its complications such as
coronary heart disease,
myocardial infarction and
stroke are the leading causes of death in the developed world.
High blood pressure, diabetes, smoking and a diet high in
cholesterol and
lipids clearly increase the likelihood of premature
atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with
vitamin E, and some of them showed that it prevents
atherosclerosis. For a long time,
vitamin E was assumed to act by decreasing the oxidation of
LDL, a key step in
atherosclerosis initiation. However, at the cellular level,
vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion,
oxLDL uptake and
cytokine production, all reactions implied in the progression of
atherosclerosis. Recent research revealed that these effects are not the result of the
antioxidant activity of
vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of
vitamin E with
enzymes and
proteins are at the basis of its non-
antioxidant effects.
Vitamin E influences the activity of several
enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase,
nitric oxide synthase,
NADPH-oxidase,
superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in
atherosclerosis (e.g.
scavenger receptors,
integrins,
selectins,
cytokines,
cyclins). These interactions promise to reveal the
biological properties of
vitamin E and allow designing better strategies for the protection against
atherosclerosis progression.