NOTCH4 and atherosclerosis: Our conclusion is based on the following observations: (i) JAG1 and NOTCH4 were exclusively enriched at LOSS regions of the aorta and were induced by LOSS in experimental flow–modified arteries, (ii) LOSS induces the expression of NOTCH4 and JAG1 and activates JAG1-NOTCH4 signaling in cultured EC, (iii) JAG1-NOTCH4 signaling represses EC subsets involved in vascular repair, and (iv) inducible deletion of Jag1 from murine EC reduced atherosclerosis at the aortic arch that contains a LOSS region.