Pulmonary hypertension (PH) is a rare disease with a poor prognosis. Increased right ventricular (RV) afterload is the most severe complication of PH, which can leads to RV fibrosis and death.

Endothelial to mesenchymal transition (EndMT) is involved in the PH development and includes transcriptional reprogramming of endothelial cells (loss of markers: vascular endothelin cadherin (VE-cadherin), leading to a shift towards mesenchymal cell phenotypes (gain of mesenchymal markers: alpha-smooth muscle actin (?-SMA), fibronectin) and a change in the composition of the extracellular matrix. Cannabidiol (CBD) is a non-intoxicating compound of Cannabis and has multidirectional beneficial properties e.g., decreasing RV systolic pressure and antifibrotic. 

The aim of the study was to investigate if CBD alleviates cardiac fibrosis by inhibiting EndMT in rats with monocrotaline (MCT)-induced PH.

The studies were done on rats with (MCT; 60 mg/kg) and without PH. CBD (10 mg/kg) or its vehicle were administered for 21 day after MCT or its vehicle administration. Western blot and immunohistochemistry methods were used.

MCT-induced PH resulted in an increase in growth transforming factor beta 1 (TGF-?1), SMAD2, phosphorylated SMAD2 (pSMAD2), fibroblasts, fibronectin, perivascular fibrosis area and ?-SMA expression, and a decrease in VE-cadherin expression. CBD reduced the expression of the TGF-?1, SMAD2, pSMAD2, fibroblasts, fibronectin and perivascular fibrosis area and increased VE-cadherin expression.

In conclusion, CBD has potential to inhibit RV remodeling, possibly by inhibiting EndMT and may be considered as an add-on therapy in the treatment of PH.