Resolution of Right Ventricular Fibrosis by a Cancer Chemotherapeutic Agent: A Novel Therapy to Treat Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) remains a fatal disease despite the availabilities of FDA‐approved vasodilators. Since right heart failure is the major cause of death among patients with PAH, new agents that can repair the damaged right ventricle (RV) have therapeutic potential. We herein report that a clinically used anti‐cancer drug, docetaxel, is capable of resolving RV fibrosis and repairing the damaged RV. Treatment of rats with SU5416 and chronic hypoxia caused PAH and severe RV damage including the occurrence of fibrosis as indicated by the accumulation of collagen. The treatment of these PAH rats with docetaxel after RV damages had developed resulted in a significant reduction of RV fibrosis with increased contractile functions. Treatment of cultured alpha‐smooth muscle actin‐expressing adult human ventricular myofibroblasts with docetaxel caused the cell death. Further, these myofibroblasts were found to have downregulated collagen 1. These results demonstrate that the docetaxel treatment results in the resolution of fibrosis and the restoration of functional cardiomyocytes in the damaged RVs in PAH animals. Mechanisms of docetaxel actions may involve the killing of myofibroblasts as well as inhibiting the collagen synthesis or promoting the collagen degradation. Targeting RV fibrosis should be considered as a therapeutic strategy for treating pulmonary arterial hypertension patients.