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SHR Neuro Cancer Cardio Lipid Metab Microb

Schaefer, AK; Kiss, A; Oszwald, A; Nagel, F; Acar, E; Aliabadi-Zuckermann, A; Hackl, M; Zuckermann, A; Kain, R; Jakubowski, A; Ferdinandy, P; Hallström, S; Podesser, BK.
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.
Transpl Int. 2022; 35: 10057 Doi: 10.3389/ti.2022.10057 [OPEN ACCESS]
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Leading authors Med Uni Graz

Hallström Seth

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Abstract:

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.

Find related publications in this database (using NLM MeSH Indexing)

Animals - administration & dosage

Fibrosis - administration & dosage

Heart Transplantation - administration & dosage

Humans - administration & dosage

Isografts - administration & dosage

Mice - administration & dosage

Mice, Inbred C57BL - administration & dosage

MicroRNAs - administration & dosage

Myocardium - administration & dosage

Serum Albumin, Human - administration & dosage

Tissue Donors - administration & dosage

Find related publications in this database (Keywords)

heart transplantation

graft preservation

cardiac isograft injury

cardiac graft fibrosis

experimental transplantation

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