Endothelial C-type natriuretic peptide maintains vascular homeostasis

Moyes, Amie J; Khambata, Rayomand S; Villar, Inmaculada Concepción; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Fernando; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Ferrer, Carlos F. Sánchez; Djordjević, Snežana; Caulfield, Mark; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

doi:10.1172/jci74281

Cited by 132 publications

(146 citation statements)

References 74 publications

(68 reference statements)

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with the recent findings of Moyes et al, who reported that CNP derived from endothelial cells plays an important role in maintaining vascular homeostasis. 31 In the present study, we found that Ach-induced, endothelium-dependent vasorelaxation was attenuated in arteries from CNP ecKO mice as compared with control mice. This impairment seems to involve NO-and prostaglandin-independent pathways, suggesting the involvement of an impaired EDHF system.…”

Section: Discussionsupporting

confidence: 53%

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

et al. 2017

View full text Add to dashboard Cite

We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell–specific CNP knockout and vascular smooth muscle cell–specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell–specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell–specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell–specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell–specific GC-B knockout mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from vascular smooth muscle cell–specific GC-B knockout mice. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B.

show abstract

Section: Discussionsupporting

confidence: 53%

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…12 Therefore, Waon therapy-mediated inhibition of aldosterone levels, or possibly attenuated oxidative stress, appears to be more pronounced in HF patients with advanced endothelial dysfunction. CNP is the 3rd member of NP family, which is mainly produced by endothelial cells and precipitates endothelial dysfunction via binding to peptide receptor C. 13 It is reported that CNP production is increased in the kidney and independently associated with poor outcomes in acute decompensated HF. 14 Notably, Ichiki et al show that CNP levels were significantly inhibited by Waon therapy in HF patients with renal impairment, suggesting that worsening renal function associated with HF (cardiorenal syndrome) could be a potential target for Waon therapy.…”

Section: Article P 709mentioning

confidence: 99%

Renin-Angiotensin-Aldosterone System and Natriuretic Peptides as Possible Targets of Waon Therapy in Heart Failure

Fukushima

Kinugawa

2017

Circ J

View full text Add to dashboard Cite

“…In addition, the expression of KLF2 was found to regulate other endothelial cell functions important for atherogenesis, including endothelial barrier function 170 , metabolism 171 , and the release of microRNAs via the shedding of endothelial microvesicles 172 . Endothelial KLF2 expression also stimulates the production of several autocoids, including NO and natriuretic-peptide C (CNP), which have been shown to be deficient in dysfunctional endothelium in vivo 173 . Furthermore, mice genetically deficient in KLF2 display enhanced atherosclerotic plaque formation when compared to wild type controls 174 .…”

Section: Introduction and Overviewmentioning

confidence: 99%

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

2016

View full text Add to dashboard Cite

Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction (ECD), in its broadest sense, encompasses a constellation of various non-adaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.

show abstract

Endothelial C-type natriuretic peptide maintains vascular homeostasis

Cited by 132 publications

References 74 publications

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

Renin-Angiotensin-Aldosterone System and Natriuretic Peptides as Possible Targets of Waon Therapy in Heart Failure

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Contact Info

Product

Resources

About