Endothelial dysfunction and angiogenesis: what is missing from COVID-19 and cannabidiol story?

Among pathways involved in the pathogenesis of coronavirus disease 2019 (COVID-19), impaired endothelial cell (EC) function and angiogenesis have been discussed less frequently than others such as cytokine storm. These two do play parts in the development of various clinical manifestations of COVID-19 including acute respiratory distress syndrome (ARDS) and the hyper-coagulation state. This narrative review attempts to gather recent data on the possible potential of cannabidiol in the treatment of COVID-19 with an eye on angiogenesis and endothelial dysfunction. Keywords including cannabidiol AND angiogenesis OR endothelial cell as well as coronavirus disease 2019 OR COVID-19 AND angiogenesis OR endothelial dysfunction were searched among the databases of PubMed and Scopus. Cannabidiol (CBD), as a therapeutic phytocannabinoid, has been approved by the Food and Drug Administration (FDA) for two types of seizures. Due to the potent anti-inflammatory properties of CBD, this compound has been suggested as a candidate treatment for COVID-19 in the literature. Although its potential effect on ECs dysfunction and pathologic angiogenesis in COVID-19 has been overlooked, other than cytokines like interleukin 1β (IL-β), IL-6, IL-8, and tumour necrosis factor α (TNFα) that are common in inflammation and angiogenesis, CBD could affect other important factors related to ECs function and angiogenesis. Data shows that CBD could decrease pathologic angiogenesis via decreasing ECs proliferation, migration, and tube formation. These activities are achieved through the suppression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), urokinase plasminogen activator (uPA), matrix metalloproteinase 2 (MMP-2), MMP-9, intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Moreover, in an animal model, ARDS and sepsis responded well to CBD treatment. Altogether and considering the current use of CBD in the clinic, the conduction of further studies on CBD administration for patients with COVID-19 seems to be useful.