The results reveal an unexpected sex disparity, with disruption of endothelial GC-B/cGMP signaling leading to diminished NO bioavailability, aortic stiffness, isolated systolic hypertension, enhanced risk of atherosclerosis, and impaired post-ischemic reparative angiogenesis in female but not in male KO mice. This evidence concerns the gene NPR2 and atherosclerosis.