Journal: American Journal of Respiratory Cell and Molecular Biology

Article Title: Role of the Aryl Hydrocarbon Receptor in Sugen 5416–induced Experimental Pulmonary Hypertension

doi: 10.1165/rcmb.2017-0260OC

Figure Lengend Snippet: Effect of the AhR antagonist CH223191 on Su/Hx pulmonary hypertension in female rats. (A) Right ventricular systolic pressure (RVSP; n = 5–6 per group), (B) right ventricular hypertrophy (RV/[LV+S]; n = 8 per group), and (C) the percentage of remodeled arteries in lungs without treatment (control) or with CH223191 alone, Su/Hx treatment with vehicle, or CH223191; n = 5–6. (D) Representative images showing elastic laminae stained with elastin/Picrosirius red. Scale bar: 20 μm. Data represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 as indicated, determined by one-way ANOVA followed by Bonferroni’s post hoc test.

Article Snippet: Stimulation with Sugen increased proliferation in BOECs ( A ); however, both the AhR antagonist CH223191 (1 μM) and Sugen 5416 (1 μM) reduced cell viability in BOECs by Trypan blue exclusion ( B ), n = 3, repeated three times.

Techniques: Control, Staining

Journal: American Journal of Respiratory Cell and Molecular Biology

Article Title: Role of the Aryl Hydrocarbon Receptor in Sugen 5416–induced Experimental Pulmonary Hypertension

doi: 10.1165/rcmb.2017-0260OC

Figure Lengend Snippet: Effect of the AhR antagonist CH223191 on the protein expression of AhR, CYP1A1, and AhR nuclear translocator (ARNT) in female rat lungs. (A) AhR expression (n = 4), (B) CYP1A1 expression, and (C) ARNT expression, with (D) representative immunoblots (n = 4–6). (E) Representative CYP1A1 immunostaining in pulmonary arteries from rats. Scale bar: 50 μm. (F) Representative AhR immunostaining in pulmonary arteries from rats. Scale bar: 50 μm. Data are shown as mean ± SEM. *P < 0.05 as indicated, determined by one-way ANOVA followed by Bonferroni’s post hoc test. HIF = hypoxia-inducible factor.

Article Snippet: Stimulation with Sugen increased proliferation in BOECs ( A ); however, both the AhR antagonist CH223191 (1 μM) and Sugen 5416 (1 μM) reduced cell viability in BOECs by Trypan blue exclusion ( B ), n = 3, repeated three times.

Techniques: Expressing, Western Blot, Immunostaining

Journal: American Journal of Respiratory Cell and Molecular Biology

Article Title: Role of the Aryl Hydrocarbon Receptor in Sugen 5416–induced Experimental Pulmonary Hypertension

doi: 10.1165/rcmb.2017-0260OC

Figure Lengend Snippet: Sugen stimulates the proliferation of blood outgrowth endothelial cells (BOECs) from female patients with PAH. Stimulation with Sugen increased proliferation in BOECs (A); however, both the AhR antagonist CH223191 (1 μM) and Sugen 5416 (1 μM) reduced cell viability in BOECs by Trypan blue exclusion (B), n = 3, repeated three times. Data are displayed as mean ± SEM. *P < 0.05, **P < 0.01 as indicated, determined by one-way ANOVA followed by Bonferroni’s post hoc test. (C) Sugen caused nuclear translocation of AhR after 60 minutes. AhR protein expression was normalized to α-tubulin and nucleoporin as markers for cytosolic and nuclear enrichment, respectively. The data are displayed as mean ± SEM. *P < 0.05 as indicated, determined by area under the curve. (D) Our data suggest that Su may activate AhR nuclear translocation and subsequent activation of CYP1A1, apoptosis, and aromatase expression. The resulting increase in E2 synthesis and metabolism may contribute to experimental PH. We also demonstrate directly that Su and hypoxia synergize, perhaps via ARNT, to cause hPASMC proliferation, suggesting that inhibition of AhR is a potential approach to the treatment of PAH.

Article Snippet: Stimulation with Sugen increased proliferation in BOECs ( A ); however, both the AhR antagonist CH223191 (1 μM) and Sugen 5416 (1 μM) reduced cell viability in BOECs by Trypan blue exclusion ( B ), n = 3, repeated three times.

Techniques: Translocation Assay, Expressing, Activation Assay, Inhibition