Similarities to hypertension seen during preeclampsia, where VEGF signaling has also been shown to be decreased by overproduction of soluble VEGFR-1 (sFlt1), have led to speculation that hypertension (and proteinuria) seen with anti-VEGF therapy may also be due to decreased VEGFR-2 signaling in EC with resultant decreased NO production, vasoconstriction and hypertension [45]. This evidence concerns the gene KDR and hypertensive disorder.