title: Genetic profiling of aortic allografts: prothymosin alpha as potential target?
abstract: Transplant arteriosclerosis is the result of intima proliferation in large vessels upon organ transplantation. Obliteration of the vascular lumen will ultimately lead to ischemia and late graft failure. Gene array analysis was performed to identify factors involved in the pathogenesis of transplant arteriosclerosis. Aortic transplants from Dark Agouti to Wistar Furth rats were performed to identify potential target genes. Hierarchical clustering of genes specifically upregulated in allogeneic but not in syngeneic aortas revealed 19 genes. A gene that fulfilled these criteria is prothymosin alpha (PTMA), a regulator of estrogen receptor transcriptional activity. PTMA gene and protein expression levels were confirmed by PCR and immunohistochemistry. Estrogen receptor staining was increased in allogeneic aortas. Furthermore, cyclin D1 a downstream target of PTMA, was also up regulated in allogeneic aortas. In conclusion, PTMA was identified as potential candidate gene involved in transplant arteriosclerosis.
authors: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Simone A
authors: SA
authors: Joosten
authors: Mieneke G A
authors: MG
authors: Smit van Dixhoorn
authors: Maria C
authors: MC
authors: Borrias
authors: Vanessa
authors: V
authors: Ham
authors: Marian J A
authors: MJ
authors: Groot Koerkamp
authors: Hanna M
authors: HM
authors: Savolainen-Peltonen
authors: Pekka
authors: P
authors: Häyry
authors: Mohamed R
authors: MR
authors: Daha
authors: Cees
authors: C
authors: Kooten
authors: Leendert C
authors: LC
authors: Paul
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology*; D019938:Cyclin D1 / Q000032:analysis; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011920:Rats, Inbred WF; D013947:Thymosin / Q000031:analogs & derivatives* / Q000032:analysis / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D011498:Protein Precursors; C040782:prothymosin alpha; D019938:Cyclin D1; D013947:Thymosin