Increased oxidative stress enhances endocannabinoid tone (671.13)

Cardiovascular disease (CVD) has been characterized as a chronic inflammatory disease that has become prevalent in industrialized societies. NADPH oxidase contributes to atherosclerosis through the activation of macrophages leading to the internalization of oxidized low-density lipoproteins (oxLDL). Chronic inflammation is caused in part by monocytes invading the vasculature leading to the formation of lipid-laden macrophage foam cells with increased flux of oxygen/nitrogen radicals and subsequent chemical modification of extracellular LDL. Endogenous cannabinoids (eCB), such as 2-arachidonoylglycerol (2-AG), may be a link between oxidative stress and atherosclerosis. We hypothesize that 2-AG biosynthesis is enhanced following CD36 ligation by oxLDL and subsequent activation of diacylglycerol lipase β (DAGLβ), the key biosynthetic enzyme of 2-AG, via upregulated NADPH oxidase activity. Treatment of murine J774 macrophages and human THP1 macrophages/monocytes with either extracellular xanthine/xanthine oxi...