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Single Donor Infusion of S-Nitroso-Human-Serum-Albumin Attenuates Cardiac Isograft Fibrosis and Preserves Myocardial Micro-RNA-126-3p in a Murine Heterotopic Heart Transplant Model.
Schaefer, Anne-Kristin; Kiss, Attila; Oszwald, André; Nagel, Felix; Acar, Eylem; Aliabadi-Zuckermann, Arezu; Hackl, Matthias; Zuckermann, Andreas; Kain, Renate; Jakubowski, Andrzej; Ferdinandy, Peter; Hallström, Seth; Podesser, Bruno K.
Afiliação
  • Schaefer AK; Ludwig Boltzmann Institute for Cardiovascular Research, Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
  • Kiss A; Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
  • Oszwald A; Ludwig Boltzmann Institute for Cardiovascular Research, Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
  • Nagel F; Department of Pathology, Medical University of Vienna, Vienna, Austria.
  • Acar E; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  • Aliabadi-Zuckermann A; Ludwig Boltzmann Institute for Cardiovascular Research, Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
  • Hackl M; Ludwig Boltzmann Institute for Cardiovascular Research, Center for Biomedical Research, Medical University of Vienna, Vienna, Austria.
  • Zuckermann A; Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
  • Kain R; TamiRNA GmbH, Vienna, Austria.
  • Jakubowski A; Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
  • Ferdinandy P; Department of Pathology, Medical University of Vienna, Vienna, Austria.
  • Hallström S; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  • Podesser BK; Department of Pharmacology, Jagiellonian University Medical College, Kraków, Poland.
Transpl Int ; 35: 10057, 2022.
Article em En | MEDLINE | ID: mdl-35497886
Objectives: Cold ischemia and subsequent reperfusion injury are non-immunologic cornerstones in the development of graft injury after heart transplantation. The nitric oxide donor S-nitroso-human-serum-albumin (S-NO-HSA) is known to attenuate myocardial ischemia-reperfusion (I/R)-injury. We assessed whether donor preservation with S-NO-HSA affects isograft injury and myocardial expression of GATA2 as well as miR-126-3p, which are considered protective against vascular and endothelial injury. Methods: Donor C57BL/6 mice received intravenous (0.1 µmol/kg/h) S-NO-HSA (n = 12), or 0.9% saline (control, n = 11) for 20 min. Donor hearts were stored in cold histidine-tryptophan-α-ketoglutarate-N solution for 12 h and underwent heterotopic, isogenic transplantation, except 5 hearts of each group, which were analysed immediately after preservation. Fibrosis was quantified and expression of GATA2 and miR-126-3p assessed by RT-qPCR after 60 days or immediately after preservation. Results: Fibrosis was significantly reduced in the S-NO-HSA group (6.47% ± 1.76 vs. 11.52% ± 2.16; p = 0.0023; 12 h-S-NO-HSA-hHTX vs. 12 h-control-hHTX). Expression of miR-126-3p was downregulated in all hearts after ischemia compared to native myocardium, but the effect was significantly attenuated when donors received S-NO-HSA (1 ± 0.27 vs. 0.33 ± 0.31; p = 0.0187; 12 h-S-NO-HSA-hHTX vs. 12 h-control-hHTX; normalized expression to U6 snRNA). Conclusion: Donor pre-treatment with S-NO-HSA lead to reduced fibrosis and preservation of myocardial miR-126-3p and GATA2 levels in murine cardiac isografts 60 days after transplantation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transplante de Coração / MicroRNAs Limite: Animals / Humans Idioma: En Revista: Transpl Int Assunto da revista: TRANSPLANTE Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Áustria

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transplante de Coração / MicroRNAs Limite: Animals / Humans Idioma: En Revista: Transpl Int Assunto da revista: TRANSPLANTE Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Áustria