Abstract 12714: Aldosterone Activates Raptor to Promote Pulmonary Artery Smooth Muscle Cell Proliferation and Pulmonary Arterial Hypertension

In pulmonary arterial hypertension (PAH), elevated levels of aldosterone (ALDO) induce a vasculopathy that is characterized by dysregulated pulmonary artery smooth muscle cell (PSMC) growth. Upregulation of the mammalian target of rapamycin complex 1 subunit Raptor induces PSMC growth; however, the factors regulating Raptor in PAH are not known. We hypothesized that Raptor activation by ALDO induces PSMC proliferation, hypertrophic vascular remodeling, and PAH. To test this hypothesis, PSMCs were exposed to vehicle (V) control or ALDO (10-7 mol/l) for 1 h. Compared to V-treated cells, ALDO increased expression of P-Raptor(Ser792) and the Raptor target P-p70S6K(Thr389) by 68% (P<0.01) and 50% (P<0.01), respectively, without affecting total Raptor/p70S6K levels. Raptor upregulation in ALDO-treated cells also increased PSMC proliferation by 19% (P<0.01), assessed by BrdU incorporation. To explore the relevance of ALDO-Raptor signaling in vivo, we studied the monocrotaline (MCT) model of PAH, which is charact...