Abstract 1158: Formation of Smooth Muscle Alpha Actin Filaments in CD34+ Bone Marrow Cells
Circulating bone marrow-derived progenitor cells can transform to vascular smooth muscle (SM)-like cells in response to arterial injury and contribute to intimal hyperplasia and atherogenesis. In this report, we present a molecular mechanism that potentially mediates the formation of SM-like cells from the CD34+ bone marrow cells in a mouse model. The mouse bone marrow contains CD34+ cells that express non-filamentous SM alpha actin. In fresh bone marrow specimens, 88 +/− 16% of CD34+ cells co-expressed SM alpha actin. The CD34+ bone marrow cells were enriched by using a magnetic bead sorting method and cultured on arterial elastic lamina and adventitial collagen specimens. The exposure to the elastic lamina specimens induced the formation of SM alpha actin filaments in 17+/−5%, 28+/− 5%, and 35+/− 8% of CD34+ bone marrow cells at day 5, 10 and 20, respectively, whereas the exposure to the collagen specimens induced SM alpha actin filament formation in a significantly reduced percentage of CD34+ bone marrow cells (5+/− 2%, 8+/− 3%, and 8+/− 4% at day 5, 10, and 20, respectively). These observations suggest that elastic laminae may stimulate the formation of SM alpha actin filaments in the CD34+ bone marrow cells. Bone marrow cells express SH2 domain-containing protein tyrosine phosphatase-1 (SHP-1), which is known to suppress cell proliferation and migration via dephosphorylating the mitogenic protein tyrosine kinases. The interaction of the CD34+ bone marrow cells with the elastic lamina specimens, but not with the adventitial collagen specimens, induced apparent SHP-1 phosphorylation. When the CD34+ bone marrow cells were transfected with SHP-1-specific siRNA, SM alpha actin filaments were found in a significantly reduced percentage of the transfected cells cultured on the elastic lamina specimens (7+ /− 3%, 9+ /− 4%, and 10+ /− 6% at day 5, 10, 20, respectively). Similar results were observed in CD34+ bone marrow cells derived from SHP-1-deficient motheaten viable mice. These observations suggest that the CD34+ bone marrow cells may serve as SM progenitor cells, the arterial elastic laminae stimulate the formation of SM alpha actin filaments in these cells, and SHP-1 potentially mediates the stimulatory effect of the arterial elastic laminae.