Endocannabinoid-like N-arachidonoyl serine is a novel pro-angiogenic mediator.

British Journal of Pharmacology
X ZhangJ E Groopman

Abstract

N-arachidonoyl serine (ARA-S) is a recently identified endocannabinoid-like lipid with weak affinity for the fully characterized cannabinoid receptors (CB(1) and CB(2)) and the transient receptor potential vanilloid receptor 1 (TRPV-1). ARA-S induces vasodilatation and shows vasoprotective potential via activation of key signalling pathways in endothelial cells. Based on these findings, the effect of ARA-S on endothelial functions was further studied. Primary human dermal microvascular endothelial cells (HMVEC) were used to investigate effects of ARA-S (0-10 microM) on certain endothelial functions, using cell proliferation, migration and wound repair models in vitro, and angiogenesis assays in vitro and ex vivo. Selective CB receptor antagonists and specific siRNAs were deployed to block individual CB receptors. We found that ARA-S stimulated angiogenesis and endothelial wound healing through induction of vascular endothelial growth factor C and its cognate receptor expression in primary HMVEC. Moreover, knock-down of G protein-coupled receptor 55 (GPR55) partly inhibited ARA-S-induced signal transduction and endothelial functions. Our results indicate that ARA-S is a pro-angiogenic factor in addition to a vessel dilator. The ...Continue Reading

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