TY - JOUR T1 - Antiproliferative effects of drugs affecting different signalling pathways on rat and human pulmonary artery smooth muscle cells JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2015.PA584 VL - 46 IS - suppl 59 SP - PA584 AU - Daniel Morales-Cano AU - Bianca Barreira AU - Virginia Chamorro AU - Rachele Pandolfi AU - Beatriz De Olaiz Navarro AU - Andrés Esteban AU - Julio Cortijo AU - Ángel Cogolludo AU - Laura Moreno AU - Francisco Pérez-Vizcaíno Y1 - 2015/09/01 UR - http://erj.ersjournals.com/content/46/suppl_59/PA584.abstract N2 - Current treatments for pulmonary arterial hypertension (PAH) include pulmonary vasodilators which may also inhibit PASMC proliferation. The aim of this study was to compare the antiproliferative effects of multiple drugs on rat and human PASMC (rPASMC and hPMASC, respectively) in vitro.rPASMCs and hPASMC were starved for 24 h, then treated with different inhibitors and incubated for 48 h in 1% foetal calf serum plus endothelin-1, 5-HT and U46619. Cell number was estimated by the MTT test.Viable cells increased by 160-180% in 48 h. Activation of the cGMP pathway with the soluble guanylyl cyclase activators riociguat and YC-1 (≤ 10 µM) or the cAMP pathway by the adenylyl cyclase activator forskolin or the prostacyclin analog teprostinil (≤ 10 µM) had no effect on proliferation. Similarly, the Rho kinase inhibitor hydroxyfasudil, the calcineurin inhibitor tacrolimus and the potassium channel opener pinacidil (all up to 10 µM) were also without effect. The phosphodiesterase 5 inhibitor sildenafil (0.1 µM), the calcium channel blocker nifedipine (1 µM) and the PPARβ agonist GW0742 (10 µM) inhibited hPASMC but not rPASMC growth. The tyrosine kinase inhibitor imatinib and the flavonoid quercetin (a pan-kinase inhibitor) reduced cell numbers in both cell types at 10 or 30 µM. This effect appears to be related, at least partly, to the induction of apoptosis.Paradoxically, a large number of drugs had no effect on proliferation at concentrations at which most of them induce a strong vasodilator effect. Human PASMC were more sensitive to inhibition than rat cells.Supported by Spanish MINECO (2011-28150) and ISCIII (CP12/03304). ER -