Endocannabinoids are unsaturated fatty acid derivatives that represent an important class of signaling lipid mediators best known for their effects in the central nervous system. It is well appreciated that endocannabinoids also have numerous effects directly on the cardiovascular system: Endocannabinoids mediate intercellular and bidirectional communication in the brain , alter the vasomotor response and cellular gene expression. The effects of endocannabinoids are largely mediated by the Gi-coupled receptors CB1 and CB2 and to some extent by nuclear receptors like PPARs, which have been shown to be activated by endocannabinoids. As endocannabinoids are released and taken up by different cells, these receptors can mediate autocrine and paracrine effects. Since many cells, including those of the vascular system, produce and degrade endocannabinoids, these compounds have become interesting targets for the treatment and prevention of cardio-vascular disease. Numerous studies have looked into the vascular consequences of a genetic knockout or activation of different endocannabinoid receptors and producing and degrading enzymes, with focus on inflammatory responses and atherosclerosis. However, the results were complex in that no unifying picture emerged. This is, in part, a consequence of the fact that the receptors all have different functions and that usually more than one endocannabinoid is produced by a cell. Depending on the presence of degrading and producing enzymes, cells can simultaneously produce 2-arachidonylglycerol (2-AG), arachidonoyl-ethanolamine (AEA), also known as anandamide, palmitoylethanolamide (PEA) and oleoylethanolamine (OEA) and each of these endocannabinoids can activate multiple receptors and signaling cascades. Therefore we are interested in identifying novel signaling mechanisms that are activated by endocannabinoids in vascular cells with aspect to epigenetic regulatory mechanisms.
Dr. Beatrice Pflüger-Müller
Tom Teichman (phd)