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Dr. Anna Ondracek and Dr. Taras Afonyushkin
MedUni Wien RESEARCHER OF THE MONTH May 2026
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Neutrophil extracellular traps (NETs) contribute to thrombus formation and inflammatory tissue injury in AMI. However, the key triggers of NET formation in AMI have remained unclear. In this study, we identified extracellular vesicles (EVs) released from activated and stressed cells as potent inducers of NETosis within the occluded coronary vessel.
This mechanism may promote a self-amplifying inflammatory cycle which aggravates vascular occlusion and subsequent cardiac dysfunction. Notably, EV-induced NET formation occurred through pathways distinct from commonly used artificial stimuli highlighting the translational relevance of our models for the identification of new inhibitors. Importantly, NET release was significantly attenuated by naturally occurring IgM antibodies targeting oxidized epitopes. Moreover, patients with higher levels of these protective IgM antibodies relative to released EV showed better cardiac function after infarction. These findings provide new mechanistic insight into immune regulation at the site of coronary occlusion. Targeting the EV–IgM axis may offer prognostic value and a promising therapeutic strategy to limit NET-driven atherothrombosis and improve outcome after AMI.
Selected Literature
Selected Publications Ondracek
- Ondracek AS▲ and Afonyushkin T▲, Aszlan A, Taqi S, Koller T, Artner T, Porsch F, Resch U, Sharma S, Scherz T, Hofbauer TM, Ozsvar-Kozma M, Seidl V, Beitzke D, Krueger M, Testori C, Lang IM, Binder CJ. Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site-derived extracellular vesicles from myocardial infarction patients. Eur Heart J. 2025 Mar 7;46(10):926-939. doi: 10.1093/eurheartj/ehae584
- Ondracek AS▲ and Aszlan A▲, Schmid M, Lenz M, Mangold A, Artner T, Emich M, Fritzer-Szekeres M, Strametz-Juranek J, Lang IM, Sponder M. Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps. Biomedicines. 2022 Nov 8;10(11):2849. doi: 10.3390/biomedicines10112849.
- Räber L, Ueki Y, Otsuka T, Losdat S, Häner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrøm T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022 May 10;327(18):1771-1781.
- Hofbauer TM▲ and Ondracek AS▲, Mangold A, Scherz T, Nechvile J, Seidl V, Brostjan C, Lang IM. Neutrophil extracellular traps induce MCP-1 at the culprit site in ST-segment elevation myocardial infarction. Front Cell Dev Biol. 2020 Nov 9;8:564169. doi: 10.3389/fcell.2020.564169
- Hofbauer TM▲ and Ondracek AS▲, Lang IM. (2020) Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis. In: Handbook of Experimental Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/164_2020_409
- Ondracek AS▲ and Hofbauer TM▲, Wurm R, Arfsten H, Seidl V, Früh A, Seidel S, Hubner P, Mangold A, Goliasch G, Heinz G, Lang IM, Sterz F, Adlbrecht C, Distelmaier K. Imbalance between plasma double-stranded DNA and deoxyribonuclease activity predicts mortality after out-of-hospital cardiac arrest. Resuscitation 2020 Apr 3;151:26-32.10.1016/ j.resuscitation.2020.03.006
- Ondracek AS, Heiden D, Oostingh GJ, Fuerst E, Fazekas J, Bergmayr C, Jensen-Jarolim E, Duschl A and Untersmayr E. Immune effects of the nitrated food allergen beta-lactoglobulin in an experimental food allergy model. Nutrients 2019, 11(10), 2463
Selected Publications Afonyushkin
- Ondracek A*, Afonyushkin T*, Aszlan A, Taqi S, Koller T, et al. Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site–derived extracellular vesicles from myocardial infarction patients. European Heart Journal, doi: 10.1093/eurheartj/ehae584. *equally contributed
- Fendl B, Weiss R, Eichhorn T, Linsberger I, Afonyushkin T, Puhm F, Binder CJ, Fischer MB, Weber V. Extracellular vesicles are associated with C-reactive protein in sepsis. Sci Rep. 2021;11:6996. doi: 10.1038/s41598-021-86489-4.
- Puhm F*, Afonyushkin T*, Resch U, Obermayer G, Rohde M, Penz T, Schuster M, Wagner G, Rendeiro AF, Melki I, Kaun C, Wojta J, Bock C, Jilma B, Mackman N, Boilard E, Binder CJ. Mitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial Cells. Circ Res. 2019;125:43-52. doi: 10.1161/ CIRCRESAHA.118.314601. *equally contributed, co-corresponding author
- Obermayer G, Afonyushkin T, Binder CJ. Oxidized low-density lipoprotein in inflammation-driven thrombosis. J Thromb Haemost. 2018;16:418-428. doi: 10.1111/jth.13925.
- Afonyushkin T, Oskolkova OV, Bochkov VN. Oxidized phospholipids stimulate production of stem cell factor via NRF2-dependent mechanisms. Angiogenesis. 2018;21:229-236. doi: 10.1007/s10456-017-9590-5.
- Afonyushkin T, Binder CJ. Extracellular Vesicles Act as Messengers of Macrophages Sensing Atherogenic Stimuli. Arterioscler Thromb Vasc Biol. 2018;38:2-3. doi: 10.1161/ATVBAHA.117.310257.
- Tsiantoulas D, Perkmann T, Afonyushkin T, Mangold A, Prohaska TA, Papac-Milicevic N, Millischer V, Bartel C, Horkko S, Boulanger CM, Tsimikas S, Fischer MB, Witztum JL, Lang IM, Binder CJ. Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies. J Lipid Res. 2015;56:440-8. doi: 10.1194/jlr.P054569.
- Schrottmaier WC, Oskolkova OV, Schabbauer G, Afonyushkin T. MicroRNA miR-320a modulates induction of HO-1, GCLM and OKL38 by oxidized phospholipids in endothelial cells. Atherosclerosis. 2014;235:1-8. doi: 10.1016/j.atherosclerosis.2014.03.026.
- Afonyushkin T, Oskolkova OV, Bochkov VN. Permissive role of miR-663 in induction of VEGF and activation of the ATF4 branch of unfolded protein response in endothelial cells by oxidized phospholipids. Atherosclerosis. 2012;225:50-5. doi: 10.1016/j.atherosclerosis.2012.06.016.
- Afonyushkin T, Oskolkova OV, Philippova M, Resink TJ, Erne P, Binder BR, Bochkov VN. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler Thromb Vasc Biol. 2010;30:1007-13. doi: 10.1161/ATVBAHA.110.204354.