Protective Effect of Triclosan in Monocrotaline-Induced Pulmonary Arterial Hypertension: FASN Inhibition a Novel Approach.

Abstract

Novel pharmacological approaches are needed to improve the outcomes of patients with idiopathic pulmonary hypertension. Fatty acid synthase (FASN) inhibitors have shown beneficial effects in preclinical models of pulmonary arterial hypertension (PAH), because of their role in the regulation of pulmonary artery vasoconstrictor tone and remodeling. We compared a Triclosan (FASN inhibitor), for the first time with the dual endothelin receptor antagonist, macitentan, in a monocrotaline-induced rat pulmonary hypertension model. Different methods (hemodynamics, histology of right ventricle and pulmonary vessels, and circulating biomarkers) showed consistently that 30 mg/kg daily of Triclosan (FASN inhibitor) and 10 mg/kg daily of macitentan slowed the progression of PAH both at the functional and structural levels. Treatments started on day 14 after monocrotaline injection and lasted 14 days. The findings of all experimental methods show that the FASN inhibitor has more similar effects as compared to macitentan. Our study reveals that inhibition of FAS decreases RV hypertrophy and improves cardiac function associated with PAH with the regulation of metabolic functions and governs further studies to establish "FASN inhibitor as a potential therapeutic approach" for the management of PAH.