Bone Marrow–Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages

Abstract

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.