CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction.
2015
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism that protects against systemic hypoxemia by redistributing blood flow from poorly to better ventilated areas of the lung, thereby minimizing ventilation-perfusion mismatch. However, in chronic hypoxemia-associated lung disease, HPV contributes to pulmonary hypertension. In this study, we provide novel evidence for a dual role of sphingolipids as important signal mediators in HPV, which critically depends on the presence of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR). CFTR gene mutations cause CF, which is associated with profound pulmonary ventilation-perfusion mismatches. The present findings propel our current understanding of HPV, establish a previously undescribed mechanism for hypoxemia in CF disease, and identify CFTR as a functional contributor to the pathologic changes in hypoxia-associated pulmonary hypertension.
Keywords:
- Cystic fibrosis
- Pulmonary artery
- Pulmonary hypertension
- Hypoxemia
- Hypoxic pulmonary vasoconstriction
- Vasoconstriction
- Immunology
- Cystic fibrosis transmembrane conductance regulator
- Lung
- Biology
- Pathology
- Internal medicine
- Hypoxia (medical)
- Pharmacology
- Sphingosine kinase 1
- Signal transduction
- TRPC6
- Endocrinology
- Rho-associated protein kinase
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