EFFECTS OF ILOPROST ON ENDOTHELIAL CELL DYSFUNCTION IN PULMONARY ARTERIAL HYPERTENSION ASSOCIATED TO SYSTEMIC SCLERODERMA: PP.6.255

2010 ◽  
Vol 28 ◽  
pp. e126
Author(s):  
R Yatsyshyn ◽  
YE Neyko ◽  
N Yatsyshyn
Keyword(s):  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systemic Scleroderma ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pulmonary Arterial

Endothelial cell dysfunction and cross talk between endothelium and smooth muscle cells in pulmonary arterial hypertension

2008 ◽  
Vol 49 (4-6) ◽  
pp. 113-118 ◽  
Author(s):  
Marc Humbert ◽  
David Montani ◽  
Frédéric Perros ◽  
Peter Dorfmüller ◽  
Serge Adnot ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Cross Talk ◽  
Muscle Cells ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pulmonary Arterial

scholarly journals Single-cell RNA-seq profiling of mouse endothelial cells in response to pulmonary arterial hypertension

2021 ◽  
Author(s):  
Julie Rodor ◽  
Shiau-Haln Chen ◽  
Jessica P Scanlon ◽  
João P Monteiro ◽  
Axelle Caudrillier ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Single Cell ◽  
Lineage Tracing ◽  
Rna Seq ◽  
Cell Dysfunction ◽  
Pulmonary Arterial ◽  
Transcriptomic Changes

Abstract Aims Endothelial cell dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterise endothelial cell (EC) dynamics in PAH at single-cell resolution. Methods and Results We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/Hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and micro-vasculature. Conclusions This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.

scholarly journals Role of Extracellular Vesicles in Pulmonary Arterial Hypertension

2020 ◽  
Vol 40 (9) ◽  
pp. 2293-2309 ◽  
Author(s):  
Avinash Khandagale ◽  
Mikael Åberg ◽  
Gerhard Wikström ◽  
Sara Bergström Lind ◽  
Ganna Shevchenko ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Extracellular Vesicles ◽  
Cell Activation ◽  
Cell Activity ◽  
Angiogenic Proteins ◽  
Pulmonary Arterial

Objective: Extracellular vesicles (EVs) have the potential to act as intercellular communicators. The aims were to characterize circulating EVs in patients with pulmonary arterial hypertension (PAH) and to explore whether these EVs contribute to endothelial activation and angiogenesis. Approach and Results: Patients with PAH (n=70) and healthy controls (HC; n=20) were included in this cross-sectional study. EVs were characterized and human pulmonary endothelial cells (hPAECs) were incubated with purified EVs. Endothelial cell activity and proangiogenic markers were analyzed. Tube formation analysis was performed for hPAECs, and the involvement of PSGL-1 (P-selectin glycoprotein ligand 1) was evaluated. The numbers of CD62P + , CD144 + , and CD235a EVs were higher in blood from PAH compared with HC. Thirteen proteins were differently expressed in PAH and HC EVs, where complement fragment C1q was the most significantly elevated protein ( P =0.0009) in PAH EVs. Upon EVs-internalization in hPAECs, more PAH compared with HC EVs evaded lysosomes ( P <0.01). As oppose to HC, PAH EVs stimulated hPAEC activation and induced transcription and translation of VEGF-A (vascular endothelial growth factor A; P <0.05) and FGF (fibroblast growth factor; P <0.005) which were released in the cell supernatant. These proangiogenic proteins were higher in patient with PAH plasma compered with HC. PAH EVs induced a complex network of angiotubes in vitro, which was abolished by inhibitory PSGL-1antibody. Anti-PSGL-1 also inhibited EV-induced endothelial cell activation and PAH EV dependent increase of VEGF-A. Conclusions: Patients with PAH have higher levels of EVs harboring increased amounts of angiogenic proteins, which induce activation of hPAECs and in vitro angiogenesis. These effects were partly because of platelet-derived EVs evasion of lysosomes upon internalization within hPAEC and through possible involvement of P-selectin-PSGL-1 pathway.

scholarly journals Immunoglobulin G anti-endothelial cell antibodies: inducers of endothelial cell apoptosis in pulmonary arterial hypertension?

2013 ◽  
Vol 174 (3) ◽  
pp. 433-440 ◽  
Author(s):  
S. J. Arends ◽  
J. G. M. C. Damoiseaux ◽  
A. M. Duijvestijn ◽  
L. Debrus-Palmans ◽  
M. Vroomen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Immunoglobulin G ◽  
Cell Apoptosis ◽  
Endothelial Cell Apoptosis ◽  
Pulmonary Arterial

scholarly journals Phenotype and function of macrophage polarization in monocrotaline-induced pulmonary arterial hypertension rat model

2021 ◽  
Author(s):  
Yong Fan ◽  
Yanjie Hao ◽  
Dai Gao ◽  
Lan Gao ◽  
Guangtao Li ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Tissue ◽  
Rat Model ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by vascular remodeling and chronic inflammation. Macrophages are the key orchestrators of inflammatory and repair responses, and have been demonstrated to be vital in the pathogenesis of PAH. However, specific phenotype of macrophage polarization (M1 & M2 macrophage) in the development of PAH and the underlying mechanisms how they work are still largely unclear. A rat model of monocrotaline (MCT) induced PAH was used. Hemodynamic analysis and histopathological experiments were conducted at day 3, 7, 14, 21 and 28, respectively. In PAH rat lung tissue, confocal microscopic images showed that CD68+NOS2+ M1-like macrophages were remarkably infiltrated on early stage, but dramatically decreased in mid-late stage. Meanwhile, CD68+CD206+ M2-like macrophages in lung tissue accumulated gradually since day 7 to day 28, and the relative ratio of M2/M1 macrophage increased over time. Results detected by western blot and immunohistochemistry were consistent. Further vitro functional studies revealed the possible mechanism involved in this pathophysiological process. By using Transwell co-culture system, it was found that M1 macrophages induced endothelial cell apoptosis, while M2 macrophages significantly promoted proliferation of both endothelial cell and smooth muscle cell. These data preliminarily demonstrated a temporal dynamic change of macrophage M1/M2 polarization status in the development of experimental PAH. M1 macrophages participated in the initial stage of inflammation by accelerating apoptosis of endothelial cell, while M2 macrophages predominated in the reparative stage of inflammation and the followed stage of aberrant tissue remodeling.

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