Abstract 11795: Smooth Muscle Cells From the Arterial Anastomosis Are the Major Precursors of Forming Neointima in Both Artery and Vein Grafts

Introduction: Smooth muscle cell (SMC) accumulation leads to neointima formation in injured vessels. Multiple sources for neointima SMCs have been found. Hypothesis: The local SMCs or their precursors from anastomosed arteries are the major contributors to neointima formation in artery or vein grafts. Methods: To identify the sources of the neointima cells, we use the Wnt1-Cre mice to label and track SMCs in the neighboring arteries and to study their contribution to neointima formation. Results: SMCs in common carotid artery were labeled with LacZ or GFP in LacZ-Stop flox /Wnt1-Cre and in RFP flox -GFP/Wnt1-Cre mice, respectively. Two graft models, vein or artery grafts, were studied. The common carotid arteries in these transgenic mice were anastomosed with donor arteries or veins from wild type mice. In artery grafts, the labeled cells in the neointima were evaluated after 1 month, > 90% of neointima cells were originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin (SMA-α) positive and expressed smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiated marker. In vein grafts, about 60% SMA-α + -cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but do costained with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in vein grafts, artery grafts, and in injured femoral arteries. Neointima SMCs showed synthetic phenotype and were positively labeled with BrdU in vitro and in vivo . Treatment with IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts. Conclusions: Our results indicate that the SMCs from neighboring artery predominate the neointima cells in vein and artery grafts. Wnt1-Cre mice could be used to explore the role of SMC from neighboring vessel in vascular remodeling.