scholarly journals Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells

2012 ◽  
Vol 53 (6) ◽  
pp. 1093-1105 ◽  
Author(s):  
Jun Ma ◽  
Lei Zhang ◽  
Weina Han ◽  
Tingting Shen ◽  
Cui Ma ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery

Beta3-adrenergic stimulation restores endothelial mitochondrial dynamics and prevents pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Oliver ◽  
S.F Rocha ◽  
M Spaczynska ◽  
D.V Lalama ◽  
M Gomez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Therapeutic Strategy ◽  
Mitochondrial Dynamics ◽  
Systolic Pressure ◽  
Funding Source ◽  
Pulmonary Arterial

Abstract Background Endothelial dysfunction is one of the most important hallmarks of pulmonary arterial hypertension (PAH). This leads to anomalous production of vasoactive mediators that are responsible for a higher vascular tone and a subsequent increase in pulmonary artery pressure (PAP), and to an increased vascular permeability that favors perivascular inflammation and remodeling, thus worsening the disease. Therefore, preservation of the endothelial barrier could become a relevant therapeutic strategy. Purpose In previous studies, others and we have suggested the pharmacological activation of the β3-adrenergic receptor (AR) as a potential therapeutic strategy for pulmonary hypertension (PH) due to left heart disease. However, its potential use in other forms of PH remain unclear. The aim of the present study was to elucidate whether the β3-AR agonist mirabegron could preserve pulmonary endothelium function and be a potential new therapy in PAH. Methods For this purpose, we have evaluated the effect of mirabegron (2 and 10 mg/kg·day) in different animal models, including the monocrotaline and the hypoxia-induced PAH models in rats and mice, respectively. Additionally, we have used a transgenic mouse model with endothelial overexpression of human β3-AR in a knockout background, and performed in vitro experiments with human pulmonary artery endothelial cells (HPAECs) for mechanistic experiments. Results Our results show a dose dependent effect of mirabegron in reducing mean PAP and Right Ventricular Systolic Pressure in both mice and rats. In addition, the use of transgenic mice has allowed us to determine that pulmonary endothelial cells are key mediators of the beneficial role of β3-AR pathway in ameliorating PAH. Mechanistically, we have shown in vitro that activation of β3-AR with mirabegron protects HPAECs from hypoxia-induced ROS production and mitochondrial fragmentation by restoring mitochondrial fission/fusion dynamics. Conclusions This protective effect of mirabegron would lead to endothelium integrity and preserved pulmonary endothelial function, which are necessary for a correct vasodilation, avoiding increased permeability and remodeling. Altogether, the current study demonstrates a beneficial effect of the β3-AR agonist mirabegron that could open new therapeutic avenues in PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Programa de Atracciόn de Talento, Comunidad de Madrid

Mechanisms by which extracellular ATP and UTP stimulate the release of prostacyclin from bovine pulmonary artery endothelial cells

1992 ◽  
Vol 1134 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Kevin D. Lustig ◽  
Laurie Erb ◽  
David M. Landis ◽  
Cathy S. Hicks-Taylor ◽  
Xiaoke Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Extracellular Atp

scholarly journals Fenfluramine-Induced Gene Dysregulation in Human Pulmonary Artery Smooth Muscle and Endothelial Cells

2011 ◽  
Vol 1 (3) ◽  
pp. 405-418 ◽  
Author(s):  
Weijuan Yao ◽  
Wenbo Mu ◽  
Amy Zeifman ◽  
Michelle Lofti ◽  
Carmelle V. Remillard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Gene Dysregulation ◽  
Pulmonary Artery Smooth Muscle ◽  
Human Pulmonary Artery

Abstract 218: Fibrinolytic Reactivity of Venous Endothelial Cells from Different Vascular Beds

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Neil G Kumar ◽  
Elisa Roztocil ◽  
John P Cullen ◽  
David L Gillespie
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Cell Types ◽  
Iliac Vein ◽  
Vein Thrombosis ◽  
Cellular Expression ◽  
Artery Embolism ◽  
Vascular Beds ◽  
Human Pulmonary Artery ◽  
Pai 1

Objective: Little is known about the molecular biology of endothelial cells from different venous vascular beds. As a result, our treatment of deep vein thrombosis (DVT) and pulmonary artery embolism (PE) remain identical. PAI-1 and tPA are important regulators of thrombosis and fibrinolysis, while ICAM-1 is known to bind fibrinogen. Here, we aim to investigate differences in fibrinolytic reactivity between human iliac vein endothelial cells (HIVECs) and human pulmonary artery endothelial cells (HPAECs). Methods: Confluent HIVECs and HPAECs, passages 3 - 6, were cultured in the absence or presence of TNFα (10 ng/mL) for 24 hours. Cellular expression of tPA and PAI-1 as analyzed by Western blot analysis and ICAM-1 as analyzed by flow cytometry were compared to controls. Results: Following TNFα stimulation, PAI-1 was upregulated in both HPAECs and HIVECs, however the upregulation observed in HPAECs was approximately 9-fold the increase observed in HIVECs (relative expression: 3.23 ± 0.52 vs 1.26 ± 0.27, n = 3, p < 0.05). While TNFα had no effect on tPA expression in HIVECs, tPA expression in HPAECS was upregulated by 33% (n = 3, p < 0.05). Although TNFα stimulation increased the number of ICAM-1 positive to approximately 100% in both cell types, a 3-fold greater increase in the Mean Fluorescence Intensity (MFI) was observed in HIVECs when compared to HPAECs (relative MFI: 69.28 ± 13.58 vs 21.92 ± 7.22, n = 3, p <0.05). Conclusions: HPAECs and HIVECs react differently in terms of fibrinolytic potential when challenged with a cytokine associated with systemic inflammation, such as in DVT and PE. These findings suggest that endothelial cells from distinct venous vascular beds may differentially regulate the fibrinolytic pathway, thus demonstrating unique properties of the deep veins and the pulmonary artery to respond to thromboembolism.

Hypoxia induces the synthesis of tropomyosin in cultured porcine pulmonary artery endothelial cells

1994 ◽  
Vol 267 (3) ◽  
pp. L271-L281 ◽  
Author(s):  
U. J. Rao ◽  
N. D. Denslow ◽  
E. R. Block
Keyword(s):  
Endothelial Cells ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Pulmonary Artery ◽  
Monolayer Culture ◽  
Cross Reactivity ◽  
Two Dimensional Gel Electrophoresis ◽  
Molecular Masses ◽  
35 Kda Protein ◽  
Porcine Pulmonary Artery

The present study examined the effect of hypoxia on protein synthesis by porcine pulmonary artery endothelial cells (PAEC). Hypoxia decreased protein synthesis in PAEC, but two-dimensional gel electrophoresis of [35S]methionine-labeled PAEC proteins demonstrated the increased synthesis of a set of proteins having molecular masses (M(r)) of 35, 36.5, 45, 116, and 205 kDa. The synthesis of the 35-, 36.5-, and 45-kDa proteins was increased in preconfluent and postconfluent cells. The 35- and 45-kDa proteins were not induced by hyperthermia, whereas the 36.5-kDa protein was induced slightly by hyperthermia. Induction of the 36.5- and 45-kDa proteins required a minimum of 8 h of hypoxia, whereas induction of the 35-kDa protein required only 4 h of exposure to hypoxia. The upregulated synthesis of the 35-, 36.5-, and 45-kDa proteins was reversible with return to normoxia. Actinomycin D, an inhibitor of transcription, did not block the hypoxic induction of the 35- and 36.5-kDa proteins but did block induction of the 45-kDa protein. The partial amino acid sequence of the 35-kDa protein obtained from cyanogen bromide cleavage of the molecule was Asp-Ala-Ile-Lys-Lys-Lys-Met-Gln-Met-Leu-Lys-Leu-Asp-Lys-Glu. This partial sequence of the 35-kDa protein identically matches the sequence of tropomyosin. Amino acid composition data and the isoelectric point (4.8) were also typical of tropomyosin. Finally, specific cross-reactivity was detected between the 35-kDa protein and a monoclonal antibody to chicken gizzard tropomyosin on immunoblot. Thus hypoxia induces the synthesis of tropomyosin, a major microfilament-associated protein, in porcine PAEC in monolayer culture.

Isolation and maintenance of human pulmonary artery endothelial cells in culture isolated from transplant donors

1994 ◽  
Vol 267 (4) ◽  
pp. L406-L413 ◽  
Author(s):  
G. A. Visner ◽  
E. D. Staples ◽  
S. E. Chesrown ◽  
E. R. Block ◽  
D. S. Zander ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Immunofluorescent Staining ◽  
Northern Analysis ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Antigen Uptake ◽  
Human Pulmonary Artery

Even though endothelial cells from different locations have similarities, there are potential morphological and functional differences between cells from different vascular regions, as well as between species. Our laboratory is interested in studying the molecular regulation of vasoactive substances in pulmonary vasculature. Therefore, we have developed reproducible methodology to isolate and maintain cultures of human pulmonary artery endothelial cells. The major innovation has been the employment of sections of pulmonary artery from heart transplant donors, from which endothelial cells are isolated. Cell monolayers were identified as endothelial cells by phase-contrast microscopy. Representative dishes of cells were further characterized by indirect immunofluorescent staining for factor VIII antigen, uptake of acetylated low-density lipoprotein, and electron microscopy. These cells were also evaluated for the expression of endothelin-1 (ET-1), a vasoactive 21-amino acid peptide derived from endothelial cells. The cells expressed ET-1 peptide and mRNA as determined by radioimmunoassay and Northern analysis, respectively. We also demonstrated that these cells are useful in transient transfection experiments for potential evaluation of promoter elements. The availability and relevance of these cells provide an important investigative tool for studies on human pulmonary vascular disease.

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