SMAD3 and pulmonary arterial hypertension: Moreover, SMAD3 has also been shown to be linked to vascular remodeling in pulmonary arterial hypertension [15].Previous studies on hyperoxia-induced lung injury have shown that SMAD3 inhibitor is involved in regulating leukocyte infiltration, fibrin deposition, activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), and the expression of MMP-2 and MMP-9 [16].