Molecular mechanisms and functional consequence of cannabidiol-induced heme oxygenase-1 and -2 expression in human endothelial cells

• Applicant: Professor Dr. Burkhard Hinz
• Subject Area: Pharmacology
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258736065

One key aspect of current cannabinoid research lies in the evaluation of the therapeutic utility of modulators of the cannabinoid system for the treatment of cardiovascular disorders. In this context the present project focusses on cannabidiol, a cannabinoid devoid of psychoactive actions that has already been approved for treatment of chronic pain in context with multiple sclerosis. On the basis of evidences for a cytoprotective action of this drug, we were able to demonstrate an inhibitory effect of cannabidiol on the spontaneous apoptosis of human umbilical vein endothelial cells (HUVEC) that was paralleled by an upregulation of the cytoprotective enzymes heme oxygenase-1 (HO-1) and -2 (HO-2). The intended research programme aims to elucidate the receptors and molecular signalling pathways of the cannabidiol-induced HO-1/HO-2 upregulation as well as its functional consequence in terms of inhibition of endothelial apoptosis and modulation of parameters involved in endothelial tissue repair such as migration and proliferation. Comparative investigations are planned using human microvascular endothelial cells, human smooth muscle cells as well as mesenchymal stem cells.

• DFG Programme: Research Grants