Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review
Abstract
:1. Introduction
2. Materials and Methods
3. Comprehensive Review
3.1. Liver Transplantation (LTx)
3.2. Kidney Transplantation (KTx)
3.3. Lung Transplantation (LuTx)
3.4. Heart Transplantation (HTx)
3.5. Possible Limitations of the Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
SOT | Solid organ transplantation |
IRI | Ischemia reperfusion injury |
RLX | Relaxin |
ECD | Extended criteria donors |
RXFP1 | Relaxin family peptide receptor 1 |
MeSH | Medical Subject Headings |
rhRLX | Recombinant human relaxin |
UW | University of Wisconsin |
SOD | Superoxide dismutase |
GR | Glucocorticoid receptor |
MDA | Malondialdehyde |
MPO | Myeloperoxidase |
NE | Neutrophil elastase |
GODT | Global Observatory on Donation and Transplantation |
LTx | Liver transplantation |
KTx | Kidney transplantation |
HTx | Heart transplantation |
LuTx | Lung transplantation |
ERK1/2 | Extracellular signal-regulated kinase-1/2 |
PI3K | Phosphatidylinositol-3 kinase |
iNOS | Inducible nitric oxide synthase |
eNOS | Endothelial nitric oxide synthase |
ROS | Reactive oxygen species |
MPTP | Mitochondrial permeability transition pore |
ET-1 | Endothelin-1 |
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Author | Organ | Experimental Animal | Intervention | RLX Application | Effect of RLX |
---|---|---|---|---|---|
Kageyama et al. [30,31] | Liver | Mice | Liver transplantation after 18 h of cold storage in UW solution without RLX. | rhRLX dose of 5 µg/kg intravenously at the onset of reperfusion. |
|
Boehnert et al. [32,33] | Liver | Rats | Isolated healthy liver perfusion model after 5 h of cold or warm ischemia in HTK solution with or without RLX. | 64 ng/mL of rhRLX was used in the preservation solution. |
|
Boehnert et al. [34] | Liver | Rats | Isolated healthy liver perfusion model after 3.5 h of cold or warm ischemia in UW solution with or without RLX. | 32 ng/mL of rhRLX was used in the reperfusion solution and 64 ng/mL of RLX in the preservation solution. |
|
Yoshida et al. [35] | Kidney | Rats | Kidney IRI model with 45 m of ischemia and 24 h of reperfusion. | 500 ng/h of porcine RLX 2 h before onset of reperfusion using an osmotic minipump under the skin. |
|
Collino et al. [36] | Kidney | Rats | Kidney IRI model with 60 m of ischemia and 6 h of reperfusion. | 5 µg/kg of rhRLX intravenously at the onset of reperfusion and again 3 h after reperfusion. |
|
Alexiou et al. [37] | Lung | Rats | Isolated healthy lung perfusion model using Krebs–Henseleit solution. Lungs exposed to 60 m of ischemia and 60 m of reperfusion. | 5 nmol/L of rhRLX in the perfusion solution. |
|
Alexiou et al. [38] | Lung | Rats | Isolated healthy lung perfusion model using Krebs–Henseleit solution. Lungs exposed to 90 m of ischemia and 90 m of reperfusion. | 5 nmol/L of rhRLX in the perfusion solution. |
|
Valle Raleigh et al. [39] | Heart | Mice (C57BL and eNOS knockout). | Heart IRI model with 30 m of ischemia and 24 h of reperfusion. | 10 µg/kg of rhRLX subcutaneously 60 m before IRI or 5 m before the onset of reperfusion. |
|
Perna et al. [40] | Heart | Pigs | Heart IRI model with 30 m of ischemia and 3 h of reperfusion. | 1.25; 2.5; or 5 μg/kg of rhRLX given upon the onset of reperfusion by a continuous infusion through the right atrial catheter. |
|
Masini et al. [41] | Heart | Rats | Heart IRI model with 30 m of ischemia and 60 m of reperfusion | 100 ng of porcine RLX dissolved in 500 μL of saline injected intravenously 30 m before ischemia. |
|
Masini et al. [42] | Heart | Guinea pigs | Isolated healthy heart perfusion model using a modified Tyrode solution supplemented by a IRI model with 20 m of ischemia and 20 m of reperfusion. | 30 ng/mL of porcine RLX in the perfusion solution |
|
Masini et al. [43] | Heart | Guinea pigs | Isolated healthy heart perfusion model using a modified Tyrode solution supplemented by a IRI model with 20 m of ischemia and 20 m of reperfusion. IRI model with 30 m of ischemia and 60 m of reperfusion was used. | 30 ng/mL of porcine RLX in the perfusion solution In the second IRI model 100 ng of porcine RLX injected intravenously 30 m before ischemia. |
|
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Jakubauskiene, L.; Jakubauskas, M.; Leber, B.; Strupas, K.; Stiegler, P.; Schemmer, P. Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review. Int. J. Mol. Sci. 2020, 21, 631. https://doi.org/10.3390/ijms21020631
Jakubauskiene L, Jakubauskas M, Leber B, Strupas K, Stiegler P, Schemmer P. Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review. International Journal of Molecular Sciences. 2020; 21(2):631. https://doi.org/10.3390/ijms21020631
Chicago/Turabian StyleJakubauskiene, Lina, Matas Jakubauskas, Bettina Leber, Kestutis Strupas, Philipp Stiegler, and Peter Schemmer. 2020. "Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review" International Journal of Molecular Sciences 21, no. 2: 631. https://doi.org/10.3390/ijms21020631