Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Bálint, Z; Zabini, D; Konya, V; Nagaraj, C; Végh, AG; Váró, G; Wilhelm, I; Fazakas, C; Krizbai, IA; Heinemann, A; Olschewski, H; Olschewski, A.
Double-stranded RNA attenuates the barrier function of human pulmonary artery endothelial cells.
PLoS One. 2014; 8(6):e63776-e63776 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Bálint Zoltán
Chandran Nagaraj
Heinemann Akos
Konya Viktoria
Olschewski Andrea
Olschewski Horst
Zabini Diana

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
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Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca(2+)) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca(2+) signaling in hPAECs by inhibiting the sarco-endoplasmic Ca(2+)-ATPase (SERCA) which is involved in the regulation of the intracellular Ca(2+) homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes.
Find related publications in this database (using NLM MeSH Indexing)
Actins - metabolism
Calcium - metabolism
Calcium-Binding Proteins - metabolism
Cell Cycle - drug effects
Cell Membrane Permeability - drug effects
Cell Proliferation - drug effects
Dextrans - metabolism
Electric Impedance -
Endothelial Cells - cytology
Fluorescein-5-isothiocyanate - analogs & derivatives
Histamine - pharmacology
Homeostasis - drug effects
Humans -
Intercellular Junctions - drug effects
Intracellular Space - drug effects
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation - drug effects
Poly I-C - pharmacology
Pulmonary Artery - cytology
RNA, Double-Stranded - pharmacology
RNA, Small Interfering - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism

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