Abstract 432: Bone Marrow-derived Cells Contribute to Vascular Lesions with Expressing Smooth Muscle Alpha Actin, but Not as Definitive Smooth Muscle Cell Lineage Expressing Smooth Muscle Myosin Heavy Chain
Background The long-standing dogma that the majority of neointimal smooth muscle cells (SMCs) are derived from preexisting medial SMCs has been recently challenged by evidences that bone marrow-derived cells in the circulating blood infiltrate the intima following vascular injury where they give rise to cells expressing SMα -actin. However, SMα -actin is not considered as a sufficient marker to define SMCs whereas it is well documented that SM myosin heavy chain (SM-MHC) is the stringent marker. The purpose of this study is to examine whether bone marrow derived cells acquire phenotypes of definitive SM lineage expressing not only SMα -actin but also SM-MHC.
Methods and Results To identify cells expressing SM-MHC and SM α-actin in vivo, we generated two mouse lines in which reporter genes were driven by the SM-MHC or SMα-actin promoter (SM-MHC+/LacZ and SMa -actin-EGFP mice). After confirmation of that transgene expression faithfully mimicked expression of the endogenous gene by comparing patterns of transgene expression in physiological and pathological conditions, wire-mediated vascular injury model was applied to wild-type mice whose bone marrow had been replaced with that from either SMα -actin-EGFP or SM-MHC+/LacZ mice and transgene expression in vascular lesions was analyzed. Although EGFP signals from bone marrow-derived SMα-actin positive cells were detected in the neointima of the mice (18.4±6.1% of cells), no cells expressing the LacZ in the neointima of the mice whose bone marrow was reconstituted by SM-MHC+/LacZ mice in even very late phase (30 weeks) after injury. Furthermore, in cardiac transplant related vasculopathy and ApoE deficient mice model, no bone marrow-derived SM-MHC positive cell was detected.
Conclusion Bone marrow-derived cells contribute to neointima formation in vascular injury models and acquire phenotypes that express SMα-actin but SM-MHC, indicating that they may not differentiate into definitive SMC lineages. Therefore, phenotypes including their function of these SMα-actin positive but SM-MHC negative cells in vascular lesions should be further elucidated.