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


Autoři: Julian Jehle aff001;  Hanna Goerich aff001;  Laura Bindila aff002;  Beat Lutz aff002;  Georg Nickenig aff001;  Vedat Tiyerili aff001
Působiště autorů: Department of Internal Medicine II Cardiology, Pneumology, Angiology, University Hospital Bonn, Bonn, Germany aff001;  Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227142

Souhrn

Objectives

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.

Methods and results

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).

Conclusions

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.

Klíčová slova:

Aorta – Blood – Catheters – Coronary arteries – Coronary heart disease – Myocardial infarction – Peas – Endocannabinoids


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2019 Číslo 12