Bubb KJ, et al. - Via in vitro and in vivo analyses, researchers focused on a central role for C-type natriuretic peptide (CNP, a fundamental endothelial signaling species that coordinates vascular homeostasis) in angiogenesis and vascular remodeling in response to ischemia. Using pulmonary microvascular endothelial cells and aortic rings isolated from wild-type, endothelium-specific CNP^–/–, global natriuretic peptide receptor (NPR)-B^–/– and NPR-C^–/– animals, and human umbilical vein endothelial cells, they assessed angiogenic capacity of CNP in vitro. Attenuated levels of CNP and its cognate NPR-C were seen in relation to clinical vascular ischemia. An attenuation was seen in the angiogenic potential of pulmonary microvascular endothelial cells, human umbilical vein endothelial cells, and isolated vessels ex vivo due to genetic or pharmacological inhibition of CNP and NPR-C, but not NPR-B. Overall, in response to ischemia, findings described a central (patho)physiological role for CNP in angiogenesis and vascular remodeling. As per data, an novel way to treat peripheral artery disease and ischemic cardiovascular disorders could be pharmacological activation of NPR-C.