Abstract
ObjectivesThe 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.Methods and results83 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).Conclusions2-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.
Highlights
Inflammation drives coronary artery disease at all stages from endothelial dysfunction, fatty streak, and foam cell formation to the thinning of the fibrous cap that precedes atherosclerotic plaque rupture and myocardial infarction [1]
Patients were divided into three groups based on their definite diagnosis of a) no coronary artery disease (CAD), b) stable CAD, or c) non-ST-segment elevation myocardial infarction (NSTEMI)
83 patients were included in this study: 15 of whom were diagnosed with NSTEMI, 48 suffered from coronary artery disease without unstable angina or elevated cardiac troponin levels, and 20 patients presented without significant stenotic coronary artery disease
Summary
Inflammation drives coronary artery disease at all stages from endothelial dysfunction, fatty streak, and foam cell formation to the thinning of the fibrous cap that precedes atherosclerotic plaque rupture and myocardial infarction [1]. The ECS is deeply involved in the initiation and progression of coronary artery disease: first, eCB control endothelial relaxation and vascular tone as shown in human and murine studies [6,7,8,9,10] Both major eCB, AEA and 2-AG have been demonstrated to promote vascular inflammation and atherogenesis in murine models [11,12,13,14]. Most studies describing the local activity of eCB within the coronary arteries have attributed their findings to systemic eCB concentrations, measured from venous blood [6, 7, 17] This major methodological flaw was first addressed by Maeda and coworkers. 2-AG was only detected in six out of 43 STEMI patients and neither eCB was detected in stable patients [18]
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