Cannabidiol Not Only Inhibits Endothelial-to-mesenchymal Transition But Also Promotes The Reverse Process Of Mesenchymal-to-endothelial Transition In An In Vitro Model

Introduction Cannabidiol (CBD) has been explored for usage in many diseases including cardiovascular complications. Endothelial-to-Mesenchymal transition (EndoMT) has been described to cause cardiac fibrosis, resulting in heart failure (HF). Here we use an in vitro model of EndoMT with Human umbilical vascular endothelial cells (HUVEC) and exhibit that CBD has an inhibitory effect on the EndoMT process. Hypothesis CBD can inhibit EndoMT Methods & Results HUVECs were used as an endothelial cell model. A combination of L-NAME and Ang II was used as EndoMT inducing agents (Figure 1. A). TGF β was used as a positive control as an established EndoMT inducing agent. When HUVECs were incubated with EndoMT inducing agents for 4 days, mesenchymal characteristics like spindle shaped cells, cytoskeleton reorganization and increase in mesenchymal marker (Vimentin) were observed. When CBD was added during EndoMT induction, the transition process was inhibited. Immunofluorescence (IF) studies exhibited a dose dependent effect of CBD in inhibiting Vimentin expression during the EndoMT process. Independently, when CBD was added to the EndoMT transitioned cells (after day 4 EndoMT), IF studies displayed a decrease in vimentin on day 8 (Figure 1. B). This demonstrates that CBD can not only inhibit EndoMT but also rescue the cells, after they underwent EndoMT and promote Mesenchymal-to-endothelial transition. Conclusion In conclusion, CBD appears to both inhibits EndoMT and promote MEndoT in transitioned cells and hence a potential impact as an antifibrotic.