Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages

Background: It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived "SM cell-like" cells. Methods and Results: Using a specific antibody against the definitive SM cell 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 although 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 were also CD115 ⁺CD11b ⁺F4/80 ⁺Ly-6C ⁺, which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b ⁺Ly-6C ⁺ bone marrow cells expressed SM α-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM α-actin ⁺ cells than in other regions. Conclusions: It appears that bone marrow-derived SM α-actin cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.