Migration of Vascular Progenitor to Intimal Hyperplasia in Transplant Arteriosclerosis Is Mediated by Monocyte Chemoattractant Protein-1
P Relliga, M Grudzinska, K Bojakowski, J Soin, C Soderberg-Naucler. Karolinska Institutet, Stockholm, Sweden; Warsaw Medical University, Warszawa, Poland
Background: Transplant arteriosclerosis is the major factor of late organ dysfunction after transplantation that involves migration of vascular progenitor cells. This process results in a progressive narrowing of the vessel lumen partly, due to a healing reaction in the intima. The aim of this study was to evaluate migration of tissue progenitor cells in transplant arteriosclerosis.
Design: To assess the clinical importance and mechanism of this infiltration, 124 myocardial biopsies from patients who received hearts from opposite-sex donors were examined for host-derived smooth muscle cells (SMCs) and inflammation. Clinical and demographic information were obtained from the patients' medical records.
Results: Host-derived SMCs accounted for 3.35 2.3% of cells in arterioles (range, 0.08%12.51%). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. Linear regression analysis showed an associated between an increased number of SMCs and the rejection grade (mean, 1.41 1.03, p = 0.034) and the number of leukocytes (19.1 12.7 [per 20 high power field], p = 0.01).The study was followed by transplantation of aorta from female F344 to male Lewis rats and collected at different time points after transplantation. Migration and activation of host-derived SMCs and cells from surrounding tissue were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR) for the SRY gene. The structures of vessels were analyzed by immunohistochemistry and electron microscopy. Moreover micro DNA assays were performed and reveal potential role of MCP1, SDF-1, RANTES and IP10 in transplant vasculopathy. The role of these factors was further analyzed in vitro and in vivo with focus on stimulation of migration of vascular progenitor. The study indicated that MCP-1 is involved in migration of vascular progenitor in transplant vasculopathy.
Conclusions: The host derive SMCs are an important source of cells that form the intimal lesion. The MCP-1 is potent chemokine for recruitment of vascular progenitor cells in the development of transplant vascular arteriosclerosis.
Tuesday, March 10, 2009 11:30 AM
Platform Session: Section H2, Tuesday Morning