Invited commentary

Abstract

According to the findings of the National Vital Statistics Report and the Morbidity and Mortality Weekly report of the Centers for Disease Control and Prevention (CDC), cardiovascular disease continues to rank high among the leading causes of morbidity and mortality in adults in the United States. It is well known that most Americans are overfed and under-exercised, but what is much less well-known is how bad nutrition is causing an alarming increase in the frequency of obesity, heart disease, stroke, cancer, diabetes, and even dementia. Several epidemiological studies suggest that dietary patterns characterized by relatively high intake of fruits and vegetables are significantly associated with reduced risks of coronary heart disease and stroke. These foods have phytochemicals including carotenoids, and polyphenols like flavonoids, resveratrol and ellagitannins, iosthiocyanates and organosulfur compounds, each of which has been shown to be associated with lower risk of cardiovascular disease. Phytochemicals are potent antioxidants and anti-inflammatory agents, thereby counteracting oxidative damage and inflammation, which underlie the pathogenesis of cardiovascular disease. The authors present more data showing the importance of a diet high in polyphenols such as ellagic acid (ellagitannins). The authors show for the first time that pretreatment of endothelial cells with ellagic acid protected against ox-LDL endothelial cell dysfunction specifically through a LOX-1- mediated signaling pathway. The proatherosclerotic role of LOX-1 was made clear by Mehta and Sawamura when they reported that a LOX-1 knockout mouse model had reduced formation of atherosclerotic lesions in a proatherogenic genetic background under a high-cholesterol diet. Proatherosclerotic and pro-oxidative signaling and inflammatory response were measured as vascular NF-κB, CD68 expression, and p38 MAPK activation. Endothelial cell function was preserved, therefore providing proof of concept that LOX-1 was proatherosclerotic. There is evidence of LOX-1-increased expression in atherosclerotic plaques from human samples. There are also interesting studies showing that patients receiving ACE inhibitors and statins (Endothelial Protection, AT1 blockage and Cholesterol-Dependent Oxidative Stress [EPAS] trial) independently and in combination had improved endothelial expression quotient of anti- and proatherosclerotic genes such as LOX-1. Further of interest is a small randomized controlled trial involving 19 patients with carotid artery stenosis found that pomegranate juice, high in ellagic acid, appeared to rescue blood pressure and carotid wall thickness. Inhibition of LOX-1 might be an interesting and novel therapeutic strategy in the treatment of atherosclerosis. One might even postulate from the authors' work that a diet high in polyphenols, especially ellagic acid, could lead to prevention of atherosclerotic disease or even regression. Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and inflammation in human endothelial cellsJournal of Vascular SurgeryVol. 52Issue 5PreviewLOX-1, a lectin-like receptor on endothelial cells, facilitates the uptake of oxidized low-density lipoprotein (oxLDL). Expression of LOX-1 is involved in the pathobiological effects of oxLDL in endothelial cells, including reactive oxygen species (ROS) generation, suppression of endothelial nitric oxide synthase (eNOS) activity, and leukocytic adhesion. Moderate consumption of phenolic-enriched food may have a protective effect against the development of atherosclerosis via the antioxidant capacity of phenolic compounds at the endothelial level. Full-Text PDF Open Archive