Abstract
Background: Exposure to hypoxia (Hx) results in upregulation of aquaporin 1 (AQP1), an integral membrane water channel protein involved in physiological processes. As shown by our previous work, hypoxia-induced expression of AQP1 affects cell migration, proliferation and apoptosis in pulmonary vascular cells and, as such, represents an interesting novel target in the pathogenesis of hypoxia-induced pulmonary hypertension (PH).
Aims and objectives: The physiological role of AQP1 in the pathogenesis of PH has not been directly addressed so far. This study was designed to characterize expression and function of AQP1 in the mouse model of hypoxia-induced PH.
Methods: The hypoxic mouse model (10% O2 for 5 weeks) was used to induce PH in vivo. To specifically target AQP1, chemically modified oligonucleotides (GapmeR) were intraperitoneally injected in mice with established PH. Hemodynamic assessment was evaluated by right heart catheterization. Expression of AQP1 in lung tissue was quantified by qPCR and Western blotting.
Results: Mice exposed to Hx developed PH. In these animals, both mRNA and protein levels of AQP1 were found to be significantly elevated compared to normoxic controls. Treatment with GapmeR targeting AQP1 significantly abated the hypoxia-induced upregulation of AQP1 and, in turn, reversed PH by decreasing right ventricular pressure to the levels of control mice.
Conclusion: Our data suggest an important functional role of AQP1 in the pathobiology of hypoxia-induced PH. These results offer novel insights in our pathogenetic understanding of the disease.
- Copyright ©the authors 2016
