500 Translationally Controlled Tumor Protein (TCTP) Revealed by Proteomic Analysis of Patient-Specific Blood outgrowth Endothelial Cells in Heritable Pulmonary Arterial Hypertension

2012 ◽  
Vol 28 (5) ◽  
pp. S284
Author(s):  
J.R. Lavoie ◽  
M. Ormiston ◽  
C. Perez-Iratxeta ◽  
B. Jiang ◽  
D.W. Courtman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Proteomic Analysis ◽  
Patient Specific ◽  
Translationally Controlled Tumor Protein ◽  
Pulmonary Arterial ◽  
Heritable Pulmonary Arterial Hypertension

A new gene for heritable pulmonary arterial hypertension: Krüppel-like factor 2

Pneumologie ◽  
2017 ◽  
Vol 71 (S 01) ◽  
pp. S1-S125
Author(s):  
C Eichstaedt ◽  
J Song ◽  
R Rodríguez Viales ◽  
Z Pan ◽  
N Benjamin ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
New Gene ◽  
Pulmonary Arterial ◽  
Heritable Pulmonary Arterial Hypertension

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

Myocardial adaptation and exercise performance in patients with pulmonary arterial hypertension assessed with patient-specific computer simulations

2021 ◽  
Vol 321 (5) ◽  
pp. H865-H880
Author(s):  
Niels Thue Olsen ◽  
Christoffer Göransson ◽  
Niels Vejlstrup ◽  
Jørn Carlsen
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Computer Simulations ◽  
Patient Specific ◽  
Limiting Factor ◽  
Myocardial Mechanics ◽  
Use Of Data ◽  
Pulmonary Arterial ◽  
Myocardial Adaptation ◽  
Rest And Exercise

Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

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