Supplementary Materials

The PDF file includes:

  • Fig. S1. Specificity of immunohistochemistry for activin A, GDF 8, and GDF 11 in human and rat lung tissue.
  • Fig. S2. Circulating activin A is elevated in WHO Group 1 PAH.
  • Fig. S3. ACTRIIA-Fc modulates GDF8-, GDF11-, activin A–, and activin B–mediated signaling in microvascular endothelial and PASMCs isolated from PH donors.
  • Fig. S4. ACTRIIA-Fc enhances BMP9-induced signaling and blocks inhibition of BMP9 signaling by GDF11 in multiple endothelial cell lineages.
  • Fig. S5. Differential basal and ligand-modulated apoptosis in PMVECs isolated from healthy and PH donors.
  • Fig. S6. No significant impact of ACTRIIA-Fc or its ligands on endothelial tube formation in PMVECs from control and PAH donors.
  • Fig. S7. Impact of ACTRIIA-Fc on ligand-mediated SMAD signaling in control and PAH-derived PASMCs.
  • Fig. S8. Modulation of smooth muscle phenotypic genes by BMP, GDF, activin, and TGFβ ligands in human PASMCs.
  • Fig. S9. Impact of ACTRIIA-Fc on proliferation and apoptosis in PASMCs isolated from both control and PH donors.
  • Fig. S10. Impact of ACTRIIA-Fc on cell migration in cultured PASMCs from healthy and PH donors.
  • Fig. S11. Treatment with ACTRIIA-Fc or sildenafil does not alter systemic arterial blood pressure in MCT-treated rats.
  • Fig. S12. Effects of ACTRIIA-Fc on cell proliferation and signaling in experimental PH.
  • Fig. S13. Treatment with ACTRIIA-Fc or sildenafil does not alter systemic arterial blood pressure in the SU-Hx rat model.
  • Fig. S14. Western blot analysis of SMAD signaling in the SU-Hx rescue model.
  • Fig. S15. Treatment with ACTRIIA-Fc improves echocardiographic measures of RV function and PH after SU-Hx exposure.
  • Fig. S16. ACTRIIA-Fc increases apoptosis in small vessels of severe obliterative PH.
  • Fig. S17. ACTRIIA-Fc normalized p-SMAD2/3 expression in the severe obliterative SU-Hx rat model.
  • Fig. S18. ACTRIIA-Fc attenuated expression of Pai-1 (Serpine1), activin A (Inhba), E-selectin (Sele), and P-selectin (Selp) mRNA in the severe obliterative SU-Hx rat model.
  • Fig. S19. Treatment of rats with ACTRIIA-Fc in the severe obliterative SU-Hx model did not affect red cell mass.
  • Table S1. Donor characteristics of serum samples used in the present study.
  • Table S2. Total number of rats and mice included in the present study.
  • Table S3. Antibodies used in the present study.
  • Table S4. Sequences of primers used in the present study.
  • Table S5. Donor characteristics of primary tissues used in the study.

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Raw data for main figures.
  • Data file S2 (Microsoft Excel format). Raw data for supplementary figures.