Rats in the urantide and MCT (monocrotaline) subgroups were injected with 10 μg/kg urantide in the urantide group or an equal amount of normal saline in the MCT group 1 week after PAH model construction in the early-treatment group and 4 weeks after the construction in the late-treatment group.
A total of 24 lncRNAs (14 upregulated and 10 down-regulated) and 82 mRNAs (17 upregulated and 65 down-regulated) were differently expressed in PAH rats induced by MCT, whereas 83 lncRNAs (59 upregulated and 24 down-regulated) and 145 mRNAs (110 upregulated and 35 down-regulated) were differently expressed after metformin treatment.
Fluoxetine dose-dependently inhibited MCT-induced pulmonary arterial hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy and reduced the S100A4 and RAGE.
In vivo, RAGE inhibition in monocrotaline- and Sugen-induced PAH demonstrates therapeutic effects characterized by PA pressure and right ventricular hypertrophy decrease (control rats have an mPAP around 15 mm Hg, PAH rats have an mPAP >40 mm Hg, and with RAGE inhibition, mPAP decreases to 20 and 28 mm Hg, respectively, in MCT and Sugen models).