Allogenic immune response promotes the accumulation of host-derived smooth muscle cells in transplant arteriosclerosis.
OBJECTIVE
Smooth muscle cells (SMCs) involved in intimal hyperplasia during transplant vasculopathy are derived both from the graft and the host. Here, the role of an allogenic immune response in the accumulation of host-derived SMCs in the neointima was explored.


METHODS
Infrarenal aorta was transplanted from female F344 to male Lewis rats with or without immunosuppression by cyclosporine A (CsA). Accumulation of host-derived SMCs and inflammatory cells in the grafts, SMC proliferation, and apoptosis were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR) for the SRY gene. Finally, SMCs were seeded in an allogenic or isogenic manner after balloon injury to carotid arteries and SMC survival was estimated.


RESULTS
Proliferating graft SMCs and infiltrating leukocytes were observed in the intima early after transplantation. In parallel, inflammatory cells and immunoglobulins infiltrated the media and apoptosis of medial SMCs occurred, leading to destruction of this layer. CsA decreased the number of SRY+ SMCs in the lesions, restricted medial destruction, and improved survival of allogenic SMCs after seeding in injured arteries.


CONCLUSIONS
Development of intimal thickenings during transplant vasculopathy involves an allogenic immune response, which promotes accumulation of host-derived SMCs and apoptosis of resident graft SMCs.
Religa
Piotr
P
Department of Surgical Sciences, Karolinska Hospital, SE-17176 Stockholm, Sweden. piotr.religa@kirurgi.ki.se
Bojakowski
Krzysztof
K
Bojakowska
Maria
M
Gaciong
Zbigniew
Z
Thyberg
Johan
J
Hedin
Ulf
U
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000637:transplantation*; D017209:Apoptosis; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology*; D005260:Female; D006789:Host vs Graft Reaction; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*