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The endocannabinoid 2-arachidonoylglycerol inhibits endothelial function and repair.
- Source :
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International journal of cardiology [Int J Cardiol] 2021 Jan 15; Vol. 323, pp. 243-250. Date of Electronic Publication: 2020 Aug 15. - Publication Year :
- 2021
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Abstract
- Background: Endothelial dysfunction promotes atherogenesis, vascular inflammation, and thrombus formation. Reendothelialization after angioplasty is required in order to prevent stent failure. Previous studies have highlighted the role of 2-arachidonoylglycerol (2-AG) in murine experimental atherogenesis and in human coronary artery disease. However, the impact of 2-AG on endothelial repair and leukocyte-endothelial cell adhesion is still unknown.<br />Methods: Endothelial repair was studied in two treatment groups of wildtype mice following electrical injury of the common carotid artery. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184, which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received DMSO (vehicle). The effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability, leukocyte-endothelial cell adhesion, surface expression of adhesion molecules, and expression of endothelial NO synthase (NOS3) was studied in vitro.<br />Results: Elevated 2-AG levels significantly impaired reendothelialization in wildtype mice following electrical injury of the common carotid artery. In vitro, 2-AG significantly reduced viability of HCAEC. Additionally, 2-AG promoted adhesion of THP-1 monocytes to HCAEC following pre-treatment of the HCAEC with 2-AG. Adhesion molecules (E-selectin, ICAM-1 and VCAM-1) remained unchanged in arterial endothelial cells, whereas 2-AG suppressed the expression of NOS3 in HCAEC.<br />Conclusion and Translational Aspect: Elevated 2-AG levels hamper endothelial repair and HCAEC proliferation, while simultaneously facilitating leukocyte-endothelial cell adhesion. Given that 2-AG is elevated in patients with coronary artery disease and non-ST-segment elevation myocardial infarction, 2-AG might decrease reendothelialization after angioplasty and thus impact the clinical outcomes.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1874-1754
- Volume :
- 323
- Database :
- MEDLINE
- Journal :
- International journal of cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 32810540
- Full Text :
- https://doi.org/10.1016/j.ijcard.2020.08.042