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. 2017 Aug 8;27(10):1195–1215. doi: 10.1038/cr.2017.87

Figure 5.

Figure 5

hCT1 attenuates the morphologic and hemodynamic effects of pulmonary arterial hypertension (PAH) in the Sugen/hypoxia (SUHx) rat model. (A) PAH was induced by administering a single subcutaneous injection of SU5416 (SU) at 20 mg/kg (VEGF receptor antagonist) followed by exposure to chronic hypoxia (Hx) at 10% oxygen for 3 weeks. Rats were recovered for 24 h in normoxia before subcutaneous implantation of osmotic minipumps containing hCT1 (6 μg/kg/h) or phosphate-buffered saline (PBS). Echocardiography was conducted and the following parameters were measured: right ventricle free wall thickness (RVFW; B), right to left ventricle internal diameter ratio (RVID:LVID; C), pulmonary artery acceleration time (PAAT; D), fractional area change (FAC; E), and cardiac output (CO; F). Control rats were not exposed to SU5416 or hypoxia. (B-F) Significant differences were observed between the PAH-induced SUHx rat groups (hCT1 or PBS) and the control rat group (n = 3; ****P < 0.0001). At 5-6 weeks, hCT1-treated SUHx animals showed a significant increase in CO (F) and FAC (E), and a decrease in RVID:LVID (C) and RVFW (B) versus the PBS-treated SUHx group (n = 3; **P < 0.01, ***P < 0.001 and ****P < 0.0001 ). (G, H) hCT1 treatment significantly increased capillary density versus PBS-treated SUHx animals (n = 3; *P < 0.05). (H) Capillaries stained with endothelial-specific CD31+ antibody followed by chromogenic detection (DAB, brown). Nuclei counterstained with Hematoxylin. Scale bar, 50 μm. (I, J) hCT1 treatment significantly decreased cardiomyocyte cross-sectional area in the right ventricle versus PBS-treated SUHx animals (n = 3; *P < 0.05). (J) Masson's Trichrome staining of heart cross-sectional area. Scale bar, 50 μm.