Interestingly, anti-Gremlin 1 antibody, while having no effect on the growth and proliferation of human PAVSMC, markedly increased not only phosphorylation of Gremlin 1 downstream effectors Smad1/5 in both, non-diseased and PAH PAVSMC, but also promoted phosphorylation of Smad2 under all tested conditions and Smad3 in diluent-treated control PAVSMC, as seen in Figure 4. Here, SMAD1 is linked to pulmonary arterial hypertension.