Ascorbate—cholesterol—lecithin interactions: factors of potential importance in the pathogenesis of atherosclerosis

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Abstract
In this review we have attempted to focus attention on some of the factors involved in the injury-repair systems of the arterial wall as well as to factors favoring the deposition of lipid at sites of injury. No effort has been made to review factors such as mechanical stress and hypertension which have a rather well-established link to the development of atherosclerosis. Likewise, it has not been possible to consider in detail events such as radiation injury or exposure to toxic drugs and chemical agents which might produce localized damage to arterial walls. However, considerable evidence is cited emphasizing the importance of intercellular glycosamino-glycans in arterial wall metabolism and the important role of ascorbic acid in the formation of these materials. Evidence is available from studies involving both humans and experimental animals, that in ascorbate deprivation, there is an accumulation of the nonsulfated polymers in the arterial wall. Such mucoid material binds plasma lipids and fibrinogen with greater affinity than do the sulfated polymers. Ascorbic acid also appears to play a significant role in cholesterol metabolism. In a number of animal experiments and in some (but not all) human studies, ascorbate is reported to have a cholesterol-lowering effect. Thus, vitamin C seems to occupy a position of unique importance by virtue of its involvement in two systems: the maintenance of vascular integrity and the metabolism of cholesterol to bile acids. This review describes certain aspects of cholesterol mobilization as related to β-unsaturated lecithins. These compounds, through the action of the enzyme lecithin: cholesterol acyltransferase, may play a key role in the formation of cholesterol esters and also aid in cholesterol transport through the formation of water-soluble systems. Although vitamin C and the lecithins are being actively promoted and widely sold in health-food stores, there have been no carefully controlled scientific evaluations of either their effectiveness or safety in statistically significant groups of humans. It is our belief that the available evidence clearly justifies, and indeed calls for, such studies.