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The proinflammatory endocannabinoid 2-arachidonoylglycerol is elevated in coronary blood from NSTEMI-patients

Session Poster session 5

Speaker Julian Jehle

Event : ESC Congress 2017

  • Topic : coronary artery disease, acute coronary syndromes, acute cardiac care
  • Sub-topic : Non-ST-Elevation Myocardial Infarction (NSTEMI)
  • Session type : Poster Session

Authors : J Jehle (Bonn,DE), H Goerich (Bonn,DE), P Pfeifer (Bonn,DE), L Bindila (Mainz,DE), B Lutz (Mainz,DE), A Zimmer (Bonn,DE), G Nickenig (Bonn,DE), V Tiyerili (Bonn,DE)

Authors:
J. Jehle1 , H. Goerich1 , P. Pfeifer1 , L. Bindila2 , B. Lutz2 , A. Zimmer3 , G. Nickenig1 , V. Tiyerili1 , 1University Hospital Bonn, Department of Cardiology - Bonn - Germany , 2Johannes Gutenberg University Mainz (JGU) - Mainz - Germany , 3University Hospital Bonn - Bonn - Germany ,

Citation:
European Heart Journal ( 2017 ) 38 ( Supplement ), 1001-1002

Background: The endocannabinoid system (ECS) modulates inflammatory processes and influences coronary circulatory function and atherogenesis in both, human and murine studies. The two main endocannabinoids (eCB), 2-AG and AEA, are known to be increased in venous blood from patients suffering from coronary artery disease (CAD). However, given their short half-life and their autocrine and paracrine mechanism of action, eCB levels in venous blood samples might not reflect arterial nor coronary eCB concentrations. This prompted us to study eCB levels in arterial blood samples drawn from distinct localisations during coronary angiography.

Methods: 60 patients undergoing coronary angiography were included in this study. Patients were divided into three groups based on their final diagnosis of a) No CAD (n=13), b) CAD (n=38) or c) NSTEMI (n=9) according to current definitions by the European Society of Cardiology. Blood was drawn from sheath and aorta in all patients and additionally from the poststenotic culprit coronary in CAD and NSTEMI patients using a 1.5 mm /10 mm OTW balloon catheter. ECB levels were assessed by liquid chromatography-multiple reaction monitoring (LC-MRM). Written informed consent was obtained from all patients. Study-specific exlusion criteria comprised acute or chronic infections and autoimmune or malignant diseases.

Results: 2-AG levels varied significantly between patient groups and between the sites of blood extraction. The lowest levels were detected in patients without CAD and in the sheath, the highest 2-AG concentrations were detected in NSTEMI patients and in the coronaries. Peripheral 2-AG levels, measured in the sheath, were significantly higher in NSTEMI patients (130.8±41.9 nmol/ml) than in CAD- (19.3±6.2 nmol/ml; p<0.001) and Non-CAD-patients (30.4±8.8 nmol/ml; p=0.01). Moreover, coronary 2-AG levels in NSTEMI-patients were significantly higher than in CAD-patients (410.8±136 nmol/ml vs. 210.7±20.5 nmol/ml; p=0.01). Intriguingly, eCB other than 2-AG did not vary between patient groups nor between the sites of blood extraction.

Conclusion: Our data reveal 2-AG to be the one eCB with the most marked local variability in arterial blood samples drawn from dictinct localisations. The striking differences in 2-AG concentrations indicate local synthesis of 2-AG, which is most marked in the coronaries of NSTEMI-patients. Possibly, local synthesis of 2-AG is effected by lesional macrophages, which thereby contribute to endothelial dysfunction and local inflammation. Decreasing local 2-AG secretion might therefore represent a promising therapeutic strategy in NSTEMI patients.

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