Priv.-Doz. Svitlana Demyanets, MD, PhD
Department of Laboratory Medicine
Waeringer-Guertel 18-20, A-1090 Vienna, Austria
Phone: +43 1 40400 53550
know-how and research interests:
→ My research interests include the role of cytokines in vascular dysfunction and obesity. Dysfunction of the vessel wall occurs in various disease processes including atherosclerosis, hypertension, peripheral artery disease, aneurysms, restenosis, transplant and diabetic vasculopathies, and is associated with risk factors such as obesity. My recent research projects investigated expression, regulation and implication of two cytokine systems, oncostatin M/glycoprotein130 and interleukin-33/ST2, in the modulation of the behavior of human endothelial, smooth muscle cells (SMCs) and adipocytes in vitro as well as in human vascular, heart and adipose tissues ex vivo and in vivo.
We could demonstrate expression of oncostatin M (OSM) in human atherosclerotic lesions obtained from patients undergoing carotid endatherectomy, which suggest an importance of OSM in vascular pathophysiology. Moreover, OSM increased production of thrombogenic plasminogen activator inhibitor-1 (PAI-1) and angiogenic vascular endothelial growth factor (VEGF) as well as enhanced cell proliferation in vascular SMCs. We also characterized signal transduction pathways, which are responsible for these effects of OSM in SMCs.
Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. We found that in human atherosclerotic tissue and human heart both IL-33 and ST2 protein is expressed by endothelial cells. Moreover, we revealed that human cardiac and vascular cells have different distribution patterns of ST2 isoforms. Furthermore, IL-33 was identified by us as an activator of human endothelial cells by increased adhesion of human leukocytes, and increased production of adhesion molecules and monocyte chemoattractant protein-1. These in vitro findings were reproducible ex vivo in human explanted atherosclerotic tissue. ST2-fusion protein and overexpression of a dominant negative form of IκB kinase 2 or IκBα, but not IL-1 receptor antagonist, abolished these effects in vitro.
My present projects aim to further characterize the role of IL-33 in atherosclerosis and obesity using both in vitro and in vivo experimental models.
research topic (general title):
Vascular inflammation: pathophysiological mechanisms and clinical significance
techniques and infrastructure of the research group:
Cell cultures and molecular biology techniques, flow cytometry, ELISA, immunohistochemistry, PCR, adhesion and proliferation assays.
5 selected publications:
Stojkovic S, Kaun C, Heinz M, Krychtiuk KA, Rauscher S, Lemberger CE, de Martin R, Gröger M, Petzelbauer P, Huk I, Huber K, Wojta J, Demyanets S. Interleukin-33 induces urokinase in human endothelial cells--possible impact on angiogenesis. J Thromb Haemost. 12(6): 948-957, 2014.
Demyanets S, Kaun C, Pentz R, Krychtiuk KA, Rauscher S, Pfaffenberger S, Zuckermann A, Aliabadi A, Gröger M, Maurer G, Huber K, Wojta J. Components of the interleukin-33/ST2 system are differentially expressed and regulated in human cardiac cells and in cells of the cardiac vasculature. J Mol Cell Cardiol. 60:16-26; 2013.
Demyanets S, Konya V, Kastl SP, Kaun C, Rauscher S, Niessner A, Pentz R, Pfaffenberger S, Rychli K, Lemberger CE, de Martin R, Heinemann A, Huk I, Gröger M, Maurer G, Huber K, Wojta J. Interleukin-33 induces expression of adhesion molecules and inflammatory activation in human endothelial cells and in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 31(9): 2080-2089, 2011.
Demyanets S, Kaun C, Rychli K, Pfaffenberger S, Kastl SP, Hohensinner PJ, Rega G, Katsaros KM, Afonyushkin T, Bochkov VN, Paireder M, Huk I, Maurer G, Huber K, Wojta J. Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves PI3K-, p38 MAPK-, Erk1/2- and STAT1/STAT3-dependent pathways and is attenuated by interferon-γ. Basic Res Cardiol. 106(2): 217-231, 2011.
Demyanets S, Kaun C, Rychli K, Rega G, Pfaffenberger S, Afonyushkin T, Bochkov VN, Maurer G, Huber K, Wojta J. The inflammatory cytokine oncostatin M induces PAI-1 in human vascular smooth muscle cells in vitro via PI 3-kinase and ERK1/2-dependent pathways. Am J Physiol Heart Circ Physiol. 293(3): H1962-8, 2007.