CORMs protect endothelial cells during cold preservation, resulting in inhibition of intimal hyperplasia after aorta transplantation in rats.
Allograft vasculopathy is the leading cause for chronic transplant loss. We investigated if the addition of carbon monoxide releasing molecules (CORMs) to the preservation solution would protect the endothelium from cold preservation injury in an aortic transplantation model. In particular, we tested if CORM preserve vascular functioning and limit neo-intima formation following cold preservation (Cp). Abdominal aortas from Lewis or Fisher rats were subjected to Cp in University of Wisconsin (UW) solution to which 50 μm of CORM-3 was added or not. Hereafter, whole mount staining, acetylcholine mediated vasorelaxation (AMV) and aortic transplantation was performed. In vitro CORM-3 protected human umbilical vein endothelial cells from Cp injury and prevented denudation and intercellular gap formation in aortic grafts. Cp resulted in loss of AMV of aorta segments. By contrast, AMV was preserved after the addition of CORM-3 during Cp. Two months after transplantation Cp of aorta grafts resulted in an increased adventitial remodelling and neo-intima formation. This was significantly blunted by CORM-3 in syngeneic recipients. Our study demonstrates that addition of CORM-3 to UW solution prevents endothelial damage, thereby maintaining vascular function directly after cold preservation. Hence, our findings might offer a novel strategy to prevent vascular damage during CP.
Vth Medical Clinic, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Hui
H
Song
Simone
S
Hoeger
Jan-Luuk
JL
Hillebrands
Isabell
I
Mandel
Ralf
R
Loesel
Grietje
G
Beck
Lothar
L
Schilling
Peter
P
Schnuelle
Benito
B
Yard
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D001807:Blood Vessel Prosthesis; D002248:Carbon Monoxide; D003080:Cold Temperature; D015925:Cryopreservation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D019188:Organ Preservation Solutions / Q000737:chemistry*; D009942:Organometallic Compounds / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020858:Tissue and Organ Harvesting / Q000379:methods*; D017539:Tunica Intima / Q000473:pathology
D019188:Organ Preservation Solutions; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002248:Carbon Monoxide