Anton Baysa

• Baysa, Anton; Maghazachi, Azzam; Sand, Kristin Larsen; Campesan, Marika; Zaglia, Tania & Mongillo, Marco [Vis alle 13 forfattere av denne artikkelen] (2022). Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 644, s. 70–78. doi: 10.1016/j.bbrc.2022.12.085. Fulltekst i vitenarkiv Vis sammendrag

  During myocardial infarction, cellular debris is released, causing a sterile inflammation via pattern recognition receptors. These reactions amplify damage and promotes secondary heart failure. The pattern recognition receptor, Toll-like receptor 9 (TLR9) detects immunogenic fragments of endogenous DNA, inducing inflammation by NFκB. The p66ShcA adaptor protein plays an important role in both ischemic myocardial damage and immune responses. We hypothesized that p66ShcA adaptor protein promotes DNA-sensing signaling via the TLR9 pathway after myocardial infarction. TLR9 protein expression increased in cardiac tissue from patients with end-stage heart failure due to ischemic heart disease. Myocardial ischemia in mice in vivo induced gene expression of key TLR9 pathway proteins (MyD88 and Unc93b1). In this model, a functional link between TLR9 and p66ShcA was revealed as; (i) ischemia-induced upregulation of TLR9 protein was abrogated in myocardium of p66ShcA knockout mice; (ii) when p66ShcA was overexpressed in NFkB reporter cells stably expressing TLR9, NFkB-activation increased during stimulation with the TLR9 agonist CpG B; (iii) in cardiac fibroblasts, p66ShcA overexpression caused TLR9 upregulation. Co-immunoprecipitation showed that ShcA proteins and TLR9 may be found in the same protein complex, which was dissipated upon TLR9 stimulation in vivo. A proximity assay confirmed the co-localization of TLR9 and ShcA proteins. The systemic immune response after myocardial ischemia was dampened in p66ShcA knockout mice as interleukin-4, -17 and −22 expression in mononuclear cells isolated from spleens was reduced. In conclusion, p66ShcA adaptor may be an interaction partner and a regulator of the TLR9 pathway post-infarction.

• Mariero, Lars Henrik; Torp, May-Kristin; Heiestad, Christina Mathisen; Baysa, Anton; Li, Yuchuan & Valen, Guro [Vis alle 8 forfattere av denne artikkelen] (2019). Inhibiting nucleolin reduces inflammation induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and reoxygenation. British Journal of Pharmacology. ISSN 0007-1188. 176(22), s. 4360–4372. doi: 10.1111/bph.14830. Fulltekst i vitenarkiv Vis sammendrag

  Background and purpose Cellular debris causes sterile inflammation after myocardial infarction. Mitochondria constitute about 30 percent of the human heart. Mitochondrial DNA (mtDNA) is a damage‐associated‐molecular‐pattern that induce injurious sterile inflammation. Little is known about mtDNA's inflammatory signalling pathways in cardiomyocytes and how mtDNA is internalized to associate with its putative receptor, toll‐like receptor 9 (TLR9). Experimental Approach We hypothesized that mtDNA can be internalized in cardiomyocytes and induce an inflammatory response. Adult mouse cardiomyocytes were exposed to hypoxia‐reoxygenation and extracellular DNA. Microscale thermophoresis was used to demonstrate binding between nucleolin and DNA. Key results Expression of the pro‐inflammatory cytokines IL‐1β and TNFα were upregulated by mtDNA, but not by nuclear DNA (nDNA), in cardiomyocytes exposed to hypoxia‐reoxygenation. Blocking the RNA/DNA binding protein nucleolin with midkine reduced expression of IL‐1β/TNFα and the nucleolin inhibitor AS1411 reduced interleukin‐6 release in adult mouse cardiomyocytes. mtDNA bound 10‐fold stronger than nDNA to nucleolin. In HEK293‐NF‐κB reporter cells, mtDNA induced NF‐κB activity in normoxia, while CpG‐DNA and hypoxia‐reoxygenation, synergistically induced TLR9‐dependent NF‐κB activity. Protein expression of nucleolin was found in the plasma membrane of cardiomyocytes and inhibition of nucleolin with midkine inhibited cellular uptake of CpG‐DNA. Inhibition of endocytosis did not reduce CpG‐DNA uptake in cardiomyocytes. Conclusion and implications mtDNA, but not nDNA, induce an inflammatory response in mouse cardiomyocytes during hypoxia‐reoxygenation. In cardiomyocytes, nucleolin is expressed on the membrane and blocking nucleolin reduce inflammation. Nucleolin might be a therapeutic target to prevent uptake of immunogenic DNA and reduce inflammation.

• Baysa, Anton; Fedorov, Anton; Kondratov, Kirill; Ruusalepp, Arno; Minasian, Sarkis & Galagudza, Michael [Vis alle 13 forfattere av denne artikkelen] (2018). Release of mitochondrial and nuclear DNA during on-pump heart surgery: Kinetics and relation to extracellular vesicles. Journal of Cardiovascular Translational Research (JCTR). ISSN 1937-5387. s. 1–9. doi: 10.1007/s12265-018-9848-3. Fulltekst i vitenarkiv
• Rutkovskiy, Arkady; Sagave, Julia Fritzi; Czibik, Gabor Tamas; Baysa, Anton; Zihlavnikova, Katarina & Hillestad, Vigdis [Vis alle 14 forfattere av denne artikkelen] (2017). Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 77(5), s. 321–331. doi: 10.1080/00365513.2017.1318447. Fulltekst i vitenarkiv
• Bliksøen, Marte; Mariero, Lars Henrik; Torp, May-Kristin; Baysa, Anton; Ytrehus, Kirsti & Haugen, Fred [Vis alle 10 forfattere av denne artikkelen] (2016). Extracellular mtDNA activates NF-κB via toll-like receptor 9 and induces cell death in cardiomyocytes. Basic Research in Cardiology. ISSN 0300-8428. 111(42). doi: 10.1007/s00395-016-0553-6. Fulltekst i vitenarkiv
• Baysa, Anton; Sagave, Julia Fritzi; Carpi, Andrea; Zaglia, Tania; Campesan, Marika & Dahl, Christen Peder [Vis alle 14 forfattere av denne artikkelen] (2015). The p66ShcA adaptor protein regulates healing after myocardial infarction. Basic Research in Cardiology. ISSN 0300-8428. 110(13). doi: 10.1007/s00395-015-0470-0. Fulltekst i vitenarkiv
• Bliksøen, Marte; Baysa, Anton; Eide, Lars; Bjørås, Magnar; Suganthan, Rajikala & Vaage, Ingvar Jarle [Vis alle 8 forfattere av denne artikkelen] (2015). Mitochondrial DNA damage and repair during ischemia-reperfusion injury of the heart. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 78, s. 9–22. doi: 10.1016/j.yjmcc.2014.11.010. Fulltekst i vitenarkiv
• Zanetti, Filippo; Carpi, Andrea; Menabo, Roberta; Giorgio, Marco; Schulz, Rainer & Valen, Guro [Vis alle 11 forfattere av denne artikkelen] (2014). The cellular prion protein counteracts cardiac oxidative stress. Cardiovascular Research (CVR). ISSN 0008-6363. 104(1), s. 93–102. doi: 10.1093/cvr/cvu194. Fulltekst i vitenarkiv
• Wu, Xueping; Sagave, Julia Fritzi; Rutkovskiy, Arkady; Haugen, Fred; Baysa, Anton & Nygård, Ståle [Vis alle 11 forfattere av denne artikkelen] (2014). Expression of bone morphogenetic protein 4 and its receptors in the remodeling heart. Life Sciences. ISSN 0024-3205. 97(2), s. 145–154. doi: 10.1016/j.lfs.2013.12.030. Fulltekst i vitenarkiv
• Lei, Peng; Baysa, Anton; Nebb, Hilde Irene; Valen, Guro; Skomedal, Tor & Osnes, Jan-Bjørn [Vis alle 8 forfattere av denne artikkelen] (2013). Activation of liver X receptors in the heart leads to accumulation of intracellular lipids and attenuation of ischemia-reperfusion injury. Basic Research in Cardiology. ISSN 0300-8428. 108. doi: 10.1007/s00395-012-0323-z. Fulltekst i vitenarkiv
• Troitskaya, Maria P.; Baysa, Anton; Vaage, Ingvar Jarle; Sand, Kristin Larsen; Maghazachi, Azzam & Valen, Guro (2012). IL-17 level is reduced during acute myocardial infarction. Role of chemokine receptor expression in monocytes and their in vitro chemotaxis towards chemokines. Toxins. 4(12), s. 1427–1439. doi: 10.3390/toxins4121427. Fulltekst i vitenarkiv
• Bilbija, Dusan; Haugen, Fred; Sagave, Julia Fritzi; Baysa, Anton; Bastani, Nasser Ezzatkhah & Levy, Finn Olav [Vis alle 9 forfattere av denne artikkelen] (2012). Retinoic Acid Signalling Is Activated in the Postischemic Heart and May Influence Remodelling. PLOS ONE. 7(9). doi: 10.1371/journal.pone.0044740. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Baysa, Anton; Sagave, Julia Fritzi; Dahl, Christen Peder; Gullestad, Lars; Carpi, Andrea & Lisa, Fabio Di [Vis alle 9 forfattere av denne artikkelen] (2012). Targeted deletion of the p66ShcA adaptor protein attenuates adverse cardiac remodeling after myocardial infarction by modulation of extracellular matrix. Cardiovascular Research (CVR). ISSN 0008-6363. 93, s. S81–S81. doi: 10.1093/cvr/cvr334. Fulltekst i vitenarkiv

Se alle arbeider i NVA