In a human phase I clinical trial of DLL4 blockade, intestinal side effects were not observed, but cardiovascular events associated with prolonged DLL4 inhibition were reported, including hypertension, pulmonary hypertension and congestive heart failure (Smith et al., 2014; Chiorean et al., 2015; Falchook et al., 2015; McKeage et al., 2018). Here, DLL4 is linked to pulmonary arterial hypertension.