Inducible and endothelial nitric oxide synthase expression during development of transplant arteriosclerosis in rat aortic grafts.
In the vascular system, distinct isoforms of nitric oxide synthase (NOS) generate nitric oxide (NO), which acts as a biological messenger. Its role in the development of transplant arteriosclerosis (TA) is still unclear. To investigate whether NO is involved in TA, we studied the expression of NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), by immunohistochemistry and in situ hybridization during the first two post-transplantation months and their relation with cold ischemia (1 to 24 hours) and reperfusion injury using an aortic transplantation model in the rat. We found an increased iNOS expression in the intima and adventitia and a decreased expression in the media, whereas eNOS expression was not significantly altered during the development of TA. Co-localization studies suggested that iNOS-positive cells were vascular smooth muscle cells, monocyte-derived macrophages, and endothelial cells. Prolonged ischemic storage time resulted in an increase in eNOS expression in the neointima. In situ hybridization showed iNOS mRNA expression by vascular cells in the neointima and media. NO produced by iNOS and eNOS may be involved, at least in part, in the pathogenesis of TA in aortic grafts. Additional studies are needed to confirm the modulatory mechanism of NO during the development of TA.
Akyürek
L M
LM
Department of Pathology, University Hospital, Uppsala, Sweden.
Fellström
B C
BC
Yan
Z Q
ZQ
Hansson
G K
GK
Funa
K
K
Larsson
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology; D014018:Tissue Distribution; D014184:Transplantation, Homologous / Q000009:adverse effects; D014185:Transplantation, Isogeneic / Q000009:adverse effects
D007527:Isoenzymes; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase