Smooth muscle cell proliferation but not neointimal formation is dependent on alloantibody in a murine model of intimal hyperplasia

B. Soleimani, A. Katopodis, G. Wieczorek, A. J.T. George, P. T. Hornick, C. Heusser

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8 Scopus citations


Transplant coronary artery disease is the pre-eminent cause of late cardiac allograft failure. It is primarily characterized by a concentric intimal hyperplasia, which we designate transplant intimal hyperplasia (TIH). Although the pathogenesis of TIH is predominately immune driven, the specific role of alloantibodies in the disease process remains undefined. In this study we investigated the contribution of alloantibodies to the development of TIH in a murine model. Orthotopic, carotid artery transplantation was performed between B10A(2R) (H-2h2) donor mice and B-cell deficient μMT-/- knockout or wild-type C57BL/6 (H-2b) recipients in the absence of immunosuppression. Grafts were harvested at 35 days and subjected to planimetry and immunohistochemistry. Alloantibodies were detectable in wild-type recipients within 7 days of transplantation and recipients developed marked TIH at 35 days. Allografts harvested from B-cell deficient recipient mice also developed TIH, which was comparable in severity with wild-type recipients. However, whereas allografts from wild-type recipients showed marked intimal smooth muscle cell (SMC) proliferation, the neointima in B-cell deficient recipients lacked SMCs. Post-transplantation administration of anti-donor serum to μMT -/- recipients restored neointimal SMC population but did not influence the severity of TIH. Significant neointimal formation occurs in the absence of alloantibodies but lacks a SMC component. Therefore, SMC migration and proliferation is antibody dependent.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalClinical and Experimental Immunology
Issue number3
StatePublished - Dec 2006

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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