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.
- muscle, smooth
- progenitor cells
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)