Temporal and spatial characterization of cellular constituents during neointimal hyperplasia after vascular injury: Potential contribution of bone-marrow-derived progenitors to arterial remodeling

Background: Exuberant smooth muscle cells (SMCs) hyperplasia is the major cause of postangioplasty restenosis. We suggested that circulating smooth muscle progenitor cells might contribute to lesion formation after vascular injury. Methods: We extensively investigated the cellular constituents during neointimal formation after mechanical vascular injury. Results: A large wire was inserted into the mouse femoral artery, causing complete enclothelial denudation and marked enlargement of the lumen with massive apoptosis of medial SMCs. At 2 h, the injured artery remained dilated with a thin media containing very few cells. A scanning electron microscopy showed fibrin and platelet deposition at the luminal side. One week after the injury, CD45-positive hematopoietic cells accumulated at the luminal side. Those CD45-positive cells gradually disappeared, whereas neointimal hyperplasia was formed with a-smooth muscle actin (SMA) positive cells. Bone marrow cells and peripheral mononuclear cells differentiated into alpha-SMA-positive cells in the presence of PDGF and basic FGF. Moreover, in bone marrow chimeric mice, bone-marrow-derived cells substantially contributed to neointimal hyperplasia after wire injury. Conclusion: These results suggest that early accumulation of hematopoietic cells may play a role in the pathogenesis of SMC hyperplasia under certain circumstances. (C) 2004 Elsevier Inc. All rights reserved.