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Increased oxidative stress enhances endocannabinoid tone (671.13)
Author(s) -
Matthews Anberitha,
Borazjani Abdolsamad,
Wang Ran,
Ross Matthew
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.671.13
Subject(s) - oxidative stress , nadph oxidase , xanthine oxidase , reactive oxygen species , chemistry , inflammation , superoxide , cd36 , biochemistry , endocrinology , medicine , enzyme , biology , receptor
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 oxidase or phorbol 12‐myristate 13‐acetate (PMA) caused an increase in superoxide (O 2 •− ) levels and enhanced 2‐AG biosynthesis (2.3‐fold and 2.8‐fold, respectively) compared to vehicle controls. These treatments were not cytotoxic. These data suggest a significant positive correlation between oxygen radical flux and 2‐AG biosynthesis in macrophages. Increased 2‐AG biosynthesis may be an adaptive response to elevated oxidative stress because of antioxidant and anti‐inflammatory actions associated with this bioactive lipid. Therefore, the pathogenesis of atherosclerosis within the vessel wall intima may be reduced by enhancing eCB tone. Grant Funding Source : Supported in part by NIH R15ES015348‐02