Abstract 5429: Bone Marrow-derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle cells (SMCs). This is based on the observation that those cells express SM α-actin; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived “SMC-like” cells. Using a specific antibody against the definitive SMC-lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM α-actin, we demonstrated that while some bone marrow-derived cells express SM α-actin in the wire injury-induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC+ bone marrow-derived cells were found in vascular lesions in apolipoprotein E−/− mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow-derived SM α-actin+ cells expressed monocyte/macrophage markers, and expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM α-actin+ cells than in other regions. In addition, flow cytometric analysis showed that bone marrow-derived SM α-actin+ cells were also CD115+ CD11b+ F4/80+ Ly6c+ CD11c−, which is the surface phenotype of inflammatory monocytes. It thus appears that bone marrow-derived cells are of monocyte/macrophage lineage and acquire a phenotype in which SMC early differentiation markers are expressed. Although these cells are involved in remodeling at active lesions in the severely injured vessel wall, it is very unlikely they acquire the definitive SMC lineage.