Apoptosis Of Medial Smooth Muscle Cells Elicits Recipient Bone Marrow Cells To Participate In Allograft Arteriosclerosis

Background:Transplant arteriosclerosis (TA) caused by chronic rejection is the major factor of chronic transplant dysfunction. Transplant arteriosclerosis is characterized by neointimal proliferation. Diffusive intimal hyperplasia modifies blood flow, ultimately leading to allograft ischemic and loss of function. Recipient bone marrow cells migrating and differentiating into vascular smooth muscle cells (VSMCs) contribute to allograft artery neointimal expansion. However, the role of medial smooth muscle cells in this process still remains to be established.Objective: To explore the biological function and its molecular mechanism of VSMCs apoptosis in the development of allograft neointimal proliferation via recipient bone marrow cells.Method and results: Aortic transplant was performed on sex-mismatched bone marrow transplantation from male SD rats to female SD rats. Lentivirus vectors carried with p53 or Bcl-XL which were promoted by specific SMC-promoter SM22αwere employed to transfect into aortic allograft. Then the aortic grafts were harvested for histological evaluation and immunohistochemistry. The results indicated that allograft artery transfected with p53 promotes medial VSMCs apoptosis and increases the expression of SDF-1αand TGF-β, subsequently induces allograft neointimal proliferation. Conversely, apoptosis of medial VSMCs inhibited by transfection of Bcl-XL reduces the expression of SDF-1αand TGF-βand decreases the neointimal formation in allograft artery. PCR assay demonstrates that apoptosis of medial VSMCs recruits recipient bone marrow cells to contribute to neointimal hyperplasia in allograft artery.Conclusion: Apoptosis of medial VSMCs promotes neointimal formation in allograft artery through recruitment and differentiation of recipient bone marrow cells.