NADPH oxidase 4 (NOX4) has an established role in the endothelium where it enhances vasodilatation and reduces blood pressure in vivo29. This oxidase generates reactive oxygen species in the endothelium and may contribute to salt sensitive hypertension in the kidney and the vasculature30–32. We found that the allele of the common variant at the NOX4 locus correlates with increased tissue specific NOX4 expression in endothelial cells rather than VSMCs (Supplementary Fig. 13c). NOX4 mediates endothelial cell apoptosis and facilitates vascular collagen synthesis contributing to endothelial dysfunction and arterial stiffness, and may explain the association with PP33,34.
