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

当前大麻素研究的一个关键方面在于评估大麻素系统调节剂治疗心血管疾病的效用。在这种情况下，目前的项目侧重于大麻二酚，一种缺乏精神活性作用的大麻素，已经被批准用于治疗多发性硬化症的慢性疼痛。基于该药物的细胞保护作用的证据，我们能够证明大麻二酚对人脐静脉内皮细胞（HUVEC）自发凋亡的抑制作用，这种抑制作用与细胞保护酶血红素加氧酶-1 （HO-1）和-2 （HO-2）的上调并行。该研究计划旨在阐明大麻二酚诱导的HO-1/HO-2上调的受体和分子信号通路，以及其在抑制内皮细胞凋亡和调节内皮组织修复（如迁移和增殖）参数方面的功能后果。计划使用人微血管内皮细胞、人平滑肌细胞和间充质干细胞进行比较研究。

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.