Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation
Uložené v:
| Názov: | Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation |
|---|---|
| Autori: | Szabo, G., Bahrle, S., Stumpf, N., Sonnenberg, K., Szabo, E. E., Pacher, P., Csont, T., Schulz, R., Dengler, T. J., Liaudet, L., Jagtap, P. G., Southan, G. J., Vahl, C. F., Hagl, S., Szabo, C. |
| Rok vydania: | 2025 |
| Zbierka: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| Predmety: | Adenosine Diphosphate/metabolism Adenosine Monophosphate/metabolism Adenosine Triphosphate/metabolism Animals Coronary Circulation Enzyme Inhibitors/*pharmacology Heart/drug effects/physiopathology *Heart Transplantation Immunohistochemistry Intercellular Adhesion Molecule-1/analysis Male Myocardial Reperfusion Injury/*prevention & control Myocardium/chemistry/metabolism/pathology P-Selectin/analysis Phenanthrenes/*pharmacology Phosphocreatine/metabolism Poly(ADP-ribose) Polymerases/*antagonists & inhibitors/metabolism Rats Rats, Inbred Lew Time Factors |
| Popis: | The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction. |
| Druh dokumentu: | article in journal/newspaper |
| Jazyk: | unknown |
| ISSN: | 1524-4571 |
| Relation: | Circulation research; https://iris.unil.ch/handle/iris/160458; serval:BIB_B7B9C02D833E; 000173386700019 |
| DOI: | 10.1161/hh0102.102657 |
| Dostupnosť: | https://iris.unil.ch/handle/iris/160458 https://doi.org/10.1161/hh0102.102657 |
| Prístupové číslo: | edsbas.F8C3C75B |
| Databáza: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction. |
|---|---|
| ISSN: | 15244571 |
| DOI: | 10.1161/hh0102.102657 |