Inflammatory response underlies Pulmonary Hypertension

Abstract

We have shown upregulation of IL‐6 mRNA, IL‐6 bioactivity and activation of PY‐STAT3, a proproliferative transcription factor in MCT‐induced pulmonary hypertension (PH), accompanied by a loss of endothelial caveolin‐1, a potent immunomodulator. To investigate the role of inflammation in hypoxia‐induced PH and compare with the MCT model, rats (¡Ö200 g) were subjected to hypobaric hypoxia or given MCT (sc, 60 mg/kg). Hemodynamic data, expression of caveolin‐1, eNOS, PY‐STAT3 were examined at 48h, 1 and 2 wks. Both models revealed progressive PH and right ventricular hypertrophy. Progressive PY‐STAT3 activation was observed at 48h, i.e. before the onset of PH (MCT, control [C], 100¡À0 vs 48h, 134¡À10*, hypoxia, C, 100¡À vs 48h, 453¡À70 *, *= P<0.05 vs C). Transient increase in eNOS expression at 1 wk was observed in both models. Unlike the MCT model, hypoxia‐induced PH did not exhibit loss of caveolin‐1. Caveolin‐1, known to inhibit PY‐STAT3 activation may be dysfunctional in the hypoxia model. In conclusion, dissimilar models of PH show activation of PY‐STAT3, indicating that inflammatory response may have a significant role in the pathogenesis of PH. (Supported in part by MF children¡ s Hosp. Res. Fund).