Unbiased assessment of 2-Arachidonoylglycerol in cardiovascular inflammation and myocardial remodeling

2-arachidonoylglycerol (2-AG) is an endogenous modulator of inflammatory processes and ligand for the endocannabinoid system. Recent scientific investigations accumulated evidences for its key role in inflammatory cardiovascular diseases, like atherosclerosis and left ventricular remodeling. However, molecular mechanisms set in motion by 2-AG are still poorly understood and its role in cardiovascular inflammation is the matter of controversial debate. Yet, there is a dramatic need to understand local effects of 2-AG at the site of heart inflammation, and tissue injury and reconstruction to develop novel therapeutic strategies which modulate both processes for the better and a fast recovery. Myeloid cells, like tissue-resident macrophages and monocytes are central mediators of inflammatory processes and mediate cardiac adverse remodelling after an insult by myocardial infarction, myocarditis or chronic hypertension. In this study, we investigated the impact of 2-AG on the transcriptional programming of peripheral monocytes as model system for resident macrophages in heart tissue or monocytes which are recruited to the site of cardiac tissue remodelling. Data of RNA sequencing analysis and quantification cytokine expression we seeked to clarify the question, if 2-AG induces rather an inflammatory or a wound healing phenotype of monocytes recruited to the site of cardiac tissue injury.