PMCID: PMC4151218Wellcome Trust (084449/Z/07/Z and 078496/Z/05/Z

Adrian J. Hobbs

Amie J. Moyes

Amrita Ahluwalia

Anne-Sophie Rebstock

Brown

Carlos F. Sánchez Ferrer

Chen

Clavell

Concepción Peiró

David L. Selwood

Fang Xiao

Fernando Rivilla

Filipa Mota

Igaki

Inmaculada Villar

Krejci

Kristen J. Bubb

Lipinski

Mark J. Caulfield

Michela I. Simone

Morley

Murthy

Natalie G. Lumsden

Paul J. Gane

Pleumeekers

Potter

Raymond J. MacAllister

Rayomand S. Khambata

Reshma S. Baliga

Roberta J. Worthington

Rose

Snezana Djordjevic

Stingo

Suga

Susana Vallejo

Trachte

Zuberi

Journal of Clinical Investigation

English

Moyes, AJ

Khambata, RS

Villar, I

Bubb, KJ

Baliga, RS

Lumsden, NG

Xiao, F

Gane, PJ

Rebstock, A-S

Worthington, RJ

Simone, MI

Mota, F

Rivilla, F

Vallejo, S

Peiro, C

Sanchez Ferrer, CF

Djordjevic, S

Caulfield, MJ

MacAllister, RJ

Selwood, DL

Ahluwalia, A

Hobbs, AJ

Queen Mary Research Online

A role of matrix metalloproteinase-8 in atherosclerosis. Circ Res.

A single-nucleotide polymorphism in C-type natriuretic peptide gene may be associated with hypertension. Hypertens Res.

Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype.

Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone.

Aneurysms of the abdominal aorta in older adults. The Rotterdam Study.

Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitment.

Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications.

C-type natriuretic peptide is a growth inhibitor of rat vascular smooth muscle cells.

C-type natriuretic peptide: the endothelial component of the natriuretic peptide system. J Cardiovasc Pharmacol. 1998;32(suppl 3):S22–S28.

Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells.

Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/ paracrine regulator from endothelial cells.

Different patterns of release of endothelium-derived relaxing factor and prostacyclin.

Drug-like properties and the causes of poor solubility and poor permeability.

Dwarfism and early death in mice lacking C-type natriuretic peptide.

Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells. Circ Res.

Endothelium-derived C-type natriuretic peptide: more than just a hyperpolarizing factor. Trends Pharmacol Sci.

Furin-mediated processing of Pro-C-type natriuretic peptide.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Influence of sex and hormone status on circulating natriuretic peptides.

Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis.

Leukocyte rolling and extravasation are severely compromised in P selectindeficient mice.

Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol.

Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol.

Natriuretic peptide receptor-3 underpins the disparate regulation of endothelial and vascular smooth muscle cell proliferation by C-type natriuretic peptide.

Natriuretic peptide system gene expression in human coronary arteries.

Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol.

Natriuretic peptides.

New insights from structural biology into the druggability of G protein-coupled receptors. Trends Pharmacol Sci.

Nitric oxide/nucleophile complexes: a unique class of nitric oxidebased vasodilators. J Cardiovasc Pharmacol. 1993;22(suppl 7):S3–S9.

Nonpeptidic ligands for peptide-activated G protein-coupled receptors. Chem Rev.

Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats.

Presence of C-type natriuretic peptide in cultured human endothelial cells and plasma.

Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages.

Receptor proteins and biological effects of C-type natriuretic peptides in the renal glomerulus of the rat.

Release of C-type natriuretic peptide accounts Coll Cardiol.

Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.

Significance of C-type natriuretic peptide (CNP) in endochondral ossification: analysis of CNP knockout mice.

Site-specific DNA recomDownloaded from http://www.jci.org on December 9, 2014. http://dx.doi.org/10.1172/JCI74281 The Journal of Clinical Investigation R e s e a R c h a R t i c l

Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.

Structure-based maximal affinity model predicts small-molecule druggability.

Suppression of atherosclerotic changes in cholesterol-fed rabbits treated with an oral inhibitor of neutral endopeptidase 24.11 (EC 3.4.24.11). Arterioscler Thromb Vasc Biol.

The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics.

Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo.

Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms.

Variable number of tandem repeat of the 5’-flanking region of type-C human natriuretic peptide receptor gene influences blood pressure levels in obesity-associated hypertension. Hypertens Res.

Endothelial C-type natriuretic peptide maintains vascular homeostasis

The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Abstract

Similar works

Full text

Available Versions

Queen Mary Research Online

University of Newcastle's Digital Repository

Crossref