Transcriptomic changes in the myocardium and coronary artery of donation after circulatory death hearts following ex vivo machine perfusion

• Verfasst von: Saemann, Lars [VerfasserIn]
• Verfasst von: Wachter, Kristina [VerfasserIn]
• Verfasst von: Georgevici, Adrian-Iustin [VerfasserIn]
• Verfasst von: Pohl, Sabine [VerfasserIn]
• Verfasst von: Hoorn, Fabio [VerfasserIn]
• Verfasst von: Veres, Gábor [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Simm, Andreas [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Transcriptomic changes in the myocardium and coronary artery of donation after circulatory death hearts following ex vivo machine perfusion
• Verf.angabe: Lars Saemann, Kristin Wächter, Adrian-Iustin Georgevici, Sabine Pohl, Fabio Hoorn, Gábor Veres, Sevil Korkmaz-Icöz, Matthias Karck, Andreas Simm, Gábor Szabó
• E-Jahr: 2024
• Jahr: 19 January 2024
• Umfang: 14 S.
• Fussnoten: Gesehen am 20.09.2024
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2024
• Band/Heft Quelle: 25(2024), 2, Artikel-ID 1261, Seite 1-14
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms25021261
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: donation after circulatory death
• Sach-SW: heart transplantation
• Sach-SW: left anterior descending
• Sach-SW: machine learning
• Sach-SW: microarrays
• Sach-SW: senescence induction
• Sach-SW: transcriptomics
• K10plus-PPN: 190307083X

Abstract

Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.