Biology of Carotenoids and their potential cardiovascular health benefits.

More than 700 carotenoids have been identified, but a few of them are considered of nutritional relevance and circulate at micromolar levels, therefore receiving most attention by health researchers. Among them, β-carotene, α-carotene and β-cryptoxanthin are the major carotenoids having significant pro-vitamin A activity, while lutein, lycopene, and zeaxanthin are not converted into active retinoids by humans. Their biological activity is therefore independent of retinoid-associated pathways. Given their chemical structure, carotenoids have been conjectured to act as free-radical scavengers, even though they can act as pro-oxidant molecules, at least at high oxygen concentration. However, more recently, several biologically beneficial activities relating to their ability to regulate various cellular functions have been proposed. Of note, a number of epidemiological studies have shown a correlation between elevated dietary carotenoid intake and circulating levels and decreased risk of cardiovascular disease (CVD). It has recently been demonstrated that circulating serum carotenoids are associated, beneficially it would seem, with markers of inflammation, oxidative stress, and endothelial dysfunction, which are known to be associated with CVD. At present, it is widely accepted that one of the earliest detectable pathogenic events in both human and experimental atherosclerosis is vascular inflammation associated with activation of NF-κB pathway, in turn triggering up-regulation of the expression of the vascular cell adhesion molecules (VCAM-1), intercellular cell adhesion molecules (ICAM-1) and E-Selectin. Nitric Oxide (NO), constitutively generated by the endothelial cells, plays an important role in maintaining vascular homeostasis and the pro-inflammatory response that characterizes the early stages of atherosclerosis. It is known that NO inhibits the vascular inflammatory response, down-regulating NF-κB-dependent expression of adhesion molecules. The maintenance of endothelial NO bioavailability is therefore considered beneficial to endothelial functions and more in general to vascular health. However, in the dysfunctional endothelium, NO may rapidly react with superoxide anion (O2-) to form a stable potent oxidant peroxynitrite (ONOO-) resulting in decreased vascular relaxation, and contributing to the up-regulation of NF-κB dependent cellular response. Thus, the general effect of anti-oxidant molecules on the biological function of NO is likely to be due, at least in part, to a direct removal of O2-. Within this scenario, carotenoids may be considered potential anti-oxidant modulators of endothelial response to pro-oxidant/inflammatory stimuli. Even though in vitro and in vivo experiments have recently demonstrated that carotenoids are able to reduce inflammation, while epidemiological studies indicate a strong correlation between dietary carotenoid consumption and decreased risk of CVD, the mechanism underlying the carotenoid’s cardiovascular protective activities, is still little known.