Search

Carotenoids are naturally occurring organic pigments that are believed to have therapeutic benefit in treating cardiovascular disease (CVD) because of their antioxidant properties. However, prospective randomized trials have failed to demonstrate a consistent benefit for the carotenoid beta-carotene in patients at risk for CVD. The basis for this apparent paradox is not well understood but may be attributed to the distinct antioxidant properties of various carotenoids resulting from their structure-dependent physicochemical interactions with biologic membranes. To test this hypothesis, we measured the effects of astaxanthin, zeaxanthin, lutein, beta-carotene, and lycopene on lipid peroxidation using model membranes enriched with polyunsaturated fatty acids. The correlative effects of these compounds on membrane structure were determined using small-angle x-ray diffraction approaches. The nonpolar carotenoids, lycopene and beta-carotene, disordered the membrane bilayer and stimulated membrane lipid peroxidation (>85% increase in lipid hydroperoxide levels), whereas astaxanthin (a polar carotenoid) preserved membrane structure and exhibited significant antioxidant activity (>40% decrease in lipid hydroperoxide levels). These results suggest that the antioxidant potential of carotenoids is dependent on their distinct membrane lipid interactions. This relation of structure and function may explain the differences in biologic activity reported for various carotenoids, with important therapeutic implications.

Statin drugs inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and share the common mechanism of lowering circulating levels of low-density lipoprotein (LDL) cholesterol, a powerful indicator of risk for cardiovascular disease. Large clinical trials have documented the benefit of hypolipidemic therapy for both primary and secondary prevention of coronary artery disease and stroke. Recent clinical findings, including direct comparator studies, now indicate that certain statins may slow progression of disease at a rate and to an extent that cannot be solely attributed to LDL reduction. The proposed mechanisms for such pleiotropic actions include enhancement of endothelial-dependent nitric oxide bioavailability, anti-inflammatory activity, and inhibition of oxidative stress. To understand the biochemical basis for such differences among statins, this article reviews their physicochemical properties and pharmacology at the molecular level.