ETA and ETB receptors contribute to neuropeptide Y-induced secretion of endothelin-1 in right but not left human ventricular endocardial endothelial cells

Endocardial endothelial cells (EECs) constitute an important component of the heart. These cells form a monolayer that covers the cavities of the right (EECRs) and left (EECLs) ventricles. They play an important role in cardiac excitation–contraction coupling via their secretion of cardioactive factors such as neuropeptide Y (NPY). They also contribute to cardiac pathology such as arrhythmia, hypertrophy, and heart failure. Differences between EECRs and EECLs contribute to tuning of circulating factors at the entry and exit of the ventricles. NPY, via activation of its receptors, modulates the excitation–secretion coupling of EECs, thus, indirectly modulating cardiac function and remodeling.

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Paracrine effects of endocardial endothelial cells on myocyte contraction mediated via endothelin

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.5.h1841 ◽

1993 ◽

Vol 265 (5) ◽

pp. H1841-H1846 ◽

Cited By ~ 19

Author(s):

A. Mebazaa ◽

E. Mayoux ◽

K. Maeda ◽

L. D. Martin ◽

E. G. Lakatta ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Vascular Endothelial Cell ◽

Myocardial Contraction ◽

Inotropic Effects ◽

Paracrine Effects ◽

Endothelin 1 ◽

Positive Inotropic Effects ◽

Endocardial Endothelial Cells ◽

Endocardial Endothelium

Endocardial endothelium is reported to modulate myocardial contraction by releasing diffusible factors, but the nature of the agent(s) responsible is unknown. In the present study we investigated the potential role of endothelin in these effects. Cultured sheep endocardial endothelial cells were found to express endothelin-1 mRNA and to release endothelin-1 into superfusing solution. This superfusate induced positive inotropic effects in isolated rat cardiac myocytes, associated with an increase in the cytosolic Ca2+ transient. Similar positive inotropic effects were induced by vascular endothelial cell superfusate as well as by synthesized endothelin-1, administered at concentrations similar to those present in the superfusate. Incubation of endocardial endothelial cell superfusate with endothelin-1-specific antiserum reduced the free endothelin-1 concentration to undetectable levels and abolished both the positive inotropic effect and the rise in cytosolic Ca2+. These findings indicate that endocardial endothelial cells may modulate myocardial contraction in part through the release of endothelin-1 and suggest that endocardial as well as vascular endothelium could exert potent paracrine effects on myocardium.

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Presence of neuropeptide Y and the Y1 receptor in the plasma membrane and nuclear envelope of human endocardial endothelial cells: modulation of intracellular calcium

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-165 ◽

2003 ◽

Vol 81 (3) ◽

pp. 288-300 ◽

Cited By ~ 45

Author(s):

Danielle Jacques ◽

Sawsan Sader ◽

Claudine Perreault ◽

Alain Fournier ◽

Georges Pelletier ◽

...

Keyword(s):

Endothelial Cells ◽

Confocal Microscopy ◽

Nuclear Envelope ◽

Neuropeptide Y ◽

Intracellular Calcium ◽

Microscopy Technique ◽

Human Fetal Heart ◽

Endocardial Endothelial Cells ◽

Npy Receptors ◽

Sustained Increase

The aims of the present study were to investigate the presence and distribution of NPY and the Y1 receptor in endocardial endothelial cells (EECs), to verify if EECs can release NPY, and to determine if the effect of NPY on intracellular calcium is mediated via the Y1 receptor. Immunofluorescence, 3-D confocal microscopy and radioimmu noassay techniques were used on 20-week-old human fetal EECs. Our results showed that NPY and the Y1 receptor are present in human EECs (hEECs) and that their distributions are similar, the fluorescence labelling being higher in the nucleus and more particularly at the level of the nuclear envelope when compared with the cytosol. Using radio immunoassay, we demonstrated that EECs are a source of NPY and can secrete this peptide upon a sustained increase of intracellular calcium ([Ca]i). Using fluo-3 and 3-D confocal microscopy technique, superfusion of hEECs as well as EECs isolated from rat adult hearts with increasing concentrations of NPY induced a dose-dependent, sustained increase in free cytosolic and nuclear Ca2+ levels. This effect of NPY on EEC [Ca]i was completely reversible upon washout of NPY and was partially blocked by BIBP3226, a selective Y1 receptor antagonist. The results suggest that NPY and Y1 receptors are present in the EECs of 20-week-old human fetal heart and they share the same distribution and localization inside the cell. In addition, EECs are able to secrete NPY in response to an increase in [Ca]i, and the Y1 receptor as well as other NPY receptors seem to participate in mediating the effects of NPY on [Ca]i in these cells. Thus, NPY released by EECs may modulate excitationsecretion coupling of these cells.Key words: neuropeptide Y (NPY), nuclear envelope receptors, endocardial endothelial cells, NPY receptors, intracellular calcium.

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Stimulation of endothelin-1 gene expression by insulin in endothelial cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54489-6 ◽

1991 ◽

Vol 266 (34) ◽

pp. 23251-23256

Author(s):

F.J. Oliver ◽

G. de la Rubia ◽

E.P. Feener ◽

M.E. Lee ◽

M.R. Loeken ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Endothelin 1 ◽

Stimulation Of

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Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)98533-9 ◽

1991 ◽

Vol 266 (24) ◽

pp. 16188-16192 ◽

Cited By ~ 3

Author(s):

M.E. Lee ◽

D.H. Temizer ◽

J.A. Clifford ◽

T. Quertermous

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Binding Protein ◽

Endothelin 1

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Ficus deltoidea enhances expression of endothelial nitric oxide synthase and reduces endothelin-1 on stimulated human coronary artery endothelial cells

Atherosclerosis ◽

10.1016/j.atherosclerosis.2016.07.762 ◽

2016 ◽

Vol 252 ◽

pp. e157-e158 ◽

Cited By ~ 1

Author(s):

R. Ahmad ◽

T. Rahman ◽

N.A. Mohd Kasim ◽

G.A. Froemming ◽

S. Muid ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Coronary Artery ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Human Coronary Artery ◽

Ficus Deltoidea ◽

Endothelin 1 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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HIV-1 Matrix Protein p17 Promotes Lymphangiogenesis and Activates the Endothelin-1/Endothelin B Receptor Axis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.113.302478 ◽

2014 ◽

Vol 34 (4) ◽

pp. 846-856 ◽

Cited By ~ 21

Author(s):

Francesca Caccuri ◽

Christine Rueckert ◽

Cinzia Giagulli ◽

Kai Schulze ◽

Daniele Basta ◽

...

Keyword(s):

Endothelial Cells ◽

Lymph Node ◽

Structure Formation ◽

Highly Active Antiretroviral Therapy ◽

Matrix Protein ◽

Lymphatic Endothelial Cells ◽

Endothelin 1 ◽

Tumor Dissemination ◽

Hiv 1

Objective— AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Approach and Results— Human primary lymph node–derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node–derived lymphatic endothelial cells and activating the Akt/extracellular signal–regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node–derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Conclusions— Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

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