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Bräsen, JH; Nieminen-Kelhä, M; Markmann, D; Malle, E; Schneider, W; Neumayer, HH; Budde, K; Luft, FC; Dragun, D.
Lectin-like oxidized low-density lipoprotein (LDL) receptor (LOX-1)-mediated pathway and vascular oxidative injury in older-age rat renal transplants.
KIDNEY INT. 2005; 67(4): 1583-1594. Doi: 10.1111/j.1523-1755.2005.00240.x [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Malle Ernst
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Abstract:
BACKGROUND: Older-age renal allografts are associated with inferior survival; however, the mechanisms are unclear. Reactive oxygen species participate in aging and in chronic vascular disease. We investigated how mediators of oxidative stress may increase allograft susceptibility to vascular injury. METHODS: We employed the low-responder allogeneic F344-to-Lew rat renal transplantation model. We used nonimmunosuppressed young (donors and recipients aged 12 weeks), old (donors and recipients aged 52 weeks), and old-to-young animal (donors aged 52 weeks and recipients aged 12 weeks) combinations. Grafts were transplanted after 2 hours cold preservation in University of Wisconsin solution and harvested 1, 2, 7 and 10 days later. Additionally, old animals receiving continuous 1.5 mg/kg cyclosporine (CyA) immunosuppression were included. Renal allograft pathology was scored according to Banff criteria. We studied intragraft vascular adhesion molecule-1 (VCAM-1), lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), and hypochlorite-modified LDL expression as well as ED-1+ monocytes/macrophages and CD8+ lymphocyte infiltration. Intragraft in situ superoxide anion radical production was determined with dihydroethidium assay on cryosections. RESULTS: During the first 2 posttransplant days, old transplants demonstrated higher functional impairment and increased oxidative stress, while young transplant had higher ED-1+ monocytes/macrophage infiltration and VCAM-1 expression. The degree of VCAM-1 expression and ED-1+ monocytes/macrophage and CD8+ lymphocyte infiltration correlated at later time points directly with the transplant age. VCAM-1 and LOX-1 staining were localized predominantly on the endothelium of arterial vessels, shifting the distribution to vascular smooth muscle layer strongly dependent on donor age and the grade of vascular injury. LOX-1 staining colocalized with hypochlorite-modified epitopes in the media of injured arteries. We measured increased in situ superoxide anion radical production in corresponding areas. Immunosuppression with CyA had no protective effect on vascular injury and LOX-1 expression. CONCLUSION: Induction of LOX-1-related oxidation pathways and increased susceptibility to oxidative stress could play an important role in promoting vascular injury in old renal transplants independent of the recipient age.
Find related publications in this database (using NLM MeSH Indexing)
Aging - physiology
Animals - physiology
Kidney - growth and development
Kidney Transplantation - pathology
Male - pathology
Models, Animal - pathology
Oxidative Stress - pathology
Rats - pathology
Rats, Inbred F344 - growth and development
Rats, Inbred Lew - growth and development
Reactive Oxygen Species - metabolism
Receptors, LDL - physiology
Receptors, Oxidized LDL - physiology
Scavenger Receptors, Class E - physiology
Transplantation, Homologous - pathology
Vascular Diseases - physiopathology

Find related publications in this database (Keywords)
VCAM-1
vascular rejection
endothelium
myeloperoxidase-hydrogen peroxide-chloride system
oxidative stress
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