Endothelial C-Type Natriuretic Peptide Is a Critical Regulator of Angiogenesis and Vascular Remodeling

作者：Kristen J. Bubb, Aisah A. Aubdool, Amie J. Moyes, Sarah J. Lewis, Jonathan P. Drayton, Owen Tang, Vedanta Mehta, Ian Zachary, David Abraham, Janice Tsui, Adrian J. Hobbs · 发表于：Circulation · 年份：2019 · DOI：10.1161/circulationaha.118.036344 · 被引用次数：96 · 研究领域：Heart Failure Treatment and Management、Pulmonary Hypertension Research and Treatments、Cardiac Fibrosis and Remodeling

Background: Angiogenesis and vascular remodeling are complementary, innate responses to ischemic cardiovascular events, including peripheral artery disease and myocardial infarction, which restore tissue blood supply and oxygenation; the endothelium plays a critical function in these intrinsic protective processes. C-type natriuretic peptide (CNP) is a fundamental endothelial signaling species that coordinates vascular homeostasis. Herein, we sought to delineate a central role for CNP in angiogenesis and vascular remodeling in response to ischemia. Methods: The in vitro angiogenic capacity of CNP was examined in 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. These studies were complemented by in vivo investigation of neovascularization and vascular remodeling after ischemia or vessel injury, and CNP/NPR-C expression and localization in tissue from patients with peripheral artery disease. Results: Clinical vascular ischemia is associated with reduced levels of CNP and its cognate NPR-C. Moreover, genetic or pharmacological inhibition of CNP and NPR-C, but not NPR-B, reduces the angiogenic potential of pulmonary microvascular endothelial cells, human umbilical vein endothelial cells, and isolated vessels ex vivo. Angiogenesis and remodeling are impaired in vivo in endothelium-specific CNP –/– and N...