Endocannabinoid 2-arachidonoylglycerol is elevated in the coronary circulation during acute coronary syndrome.

<h4>Objectives</h4>The endocannabinoid system modulates coronary circulatory function and atherogenesis. The two major endocannabinoids (eCB), 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (AEA), are increased in venous blood from patients with coronary artery disease (CAD...

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Main Authors: Julian Jehle, Hanna Goerich, Laura Bindila, Beat Lutz, Georg Nickenig, Vedat Tiyerili
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0227142&type=printable
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Summary:<h4>Objectives</h4>The endocannabinoid system modulates coronary circulatory function and atherogenesis. The two major endocannabinoids (eCB), 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (AEA), are increased in venous blood from patients with coronary artery disease (CAD). However, given their short half-life and their autocrine/paracrine mechanism of action, eCB levels in venous blood samples might not reflect arterial or coronary eCB concentrations. The aim of this cross-sectional study was to identify the local concentration profile of eCB and to detect whether and how this concentration profile changes in CAD and NSTEMI versus patients without CAD.<h4>Methods and results</h4>83 patients undergoing coronary angiography were included in this study. Patients were divided into three groups based on their definite diagnosis of a) no CAD, b) stable CAD, or c) non-ST-segment elevation myocardial infarction (NSTEMI). Blood was drawn from the arterial sheath and the aorta in all patients and additionally distal to the culprit coronary lesion in CAD- and NSTEMI patients. 2-AG levels varied significantly between patient groups and between the sites of blood extraction. The lowest levels were detected in patients without CAD; the highest 2-AG concentrations were detected in NSTEMI patients and in the coronary arteries. Peripheral 2-AG levels were significantly higher in NSTEMI patients (107.4 ± 28.4 pmol/ml) than in CAD- (17.4 ± 5.4 pmol/ml; p < 0.001), or no-CAD patients (23.9 ± 7.1 pmol/ml; p < 0.001). Moreover, coronary 2-AG levels were significantly higher in NSTEMI patients than in CAD patients (369.3 ± 57.2 pmol/ml vs. 240.1 ± 25.3 pmol/ml; p = 0.024).<h4>Conclusions</h4>2-AG showed significant variability in arterial blood samples drawn from distinct locations. Possibly, lesional macrophages synthesise 2-AG locally, which thereby contributes to endothelial dysfunction and local inflammation.
ISSN:1932-6203