Deregulated hypoxic response in myeloid cells: A model for high‐altitude pulmonary oedema (HAPE)

AIM High altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary edema rather than as a causative factor. In this study we aim to understand the role of hypoxic response in myeloid cells and its involvement in pathogenesis of HAPE. METHODS We have generated a conditional deletion in mice of the von Hippel-Lindau factor (VHL) in myeloid cells to determine the effect of a deregulated hypoxic response in pulmonary edema. RESULTS The deletion of VHL in pulmonary myeloid cells gave rise to pulmonary edema, increased pulmonary vascular permeability, and reduced performance during exertion. These changes were accompanied by reduced stroke volume in the left ventricle. CONCLUSION In this model we show that a deregulated myeloid cell hypoxic response can trigger some of the most important symptoms of HAPE and thus mice with a deletion of VHL in the myeloid lineage can function as a model of HAPE.