Copyright © 2004, European Society of Cardiology
Allogenic immune response promotes the accumulation of host-derived smooth muscle cells in transplant arteriosclerosis
aDepartment of Surgical Sciences, Karolinska Hospital, SE-17176 Stockholm, Sweden
bDepartment of Internal Medicine and Hypertension, Medical University of Warsaw, Warsaw, Poland
cDepartment of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden
* Corresponding author. Department of Surgical Sciences, Karolinska Hospital, SE-17176 Stockholm, Sweden. Email address: piotr.religa{at}kirurgi.ki.se
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.
KEYWORDS Transplantation; Smooth muscle; Remodelling; Progenitor; Apoptosis
Time for primary review 21 days
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