In vivo , KLF5 inhibition reverses PAH development. A) Mean PA pressure was measured on closed chest rats by right catheterization. The mean PA pressure is increased significantly in PAH, whereas KLF5 and STAT3 inhibition (siRNA) decrease the pulmonary pressure. The right ventricular hypertrophy, evaluated by Fulton index measurement, is reversed with KLF5 and STAT3 inhibition. Pulmonary Vascular Resistances (PVR) are increased in PAH rats and KLF5 or STAT3 inhibition decreased them. B) KLF5 activation has been evaluated in distal pulmonary arteries from rats by immunofluorescence. Nuclear colocalization of KLF5 is increased in PAH-PASMC from distal PA compared to healthy PA and KLF5 and STAT3 inhibition decrease KLF5 translocation. Proliferation and apoptosis have been evaluated by immunofluorescence (respectively by Ki67 and TUNEL). Proliferation increases in PAH-PA compared to control PA was decreased after treatment with siKLF5 or siSTAT3. Apoptosis resistance of the PA-PAH is reversed after KLF5 and STAT3 inhibition (*, P < 0.05; **, P < 0.01; ***, P < 0.001).