c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1+ Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin

Objective—Vascular smooth muscle cells (VSMCs) are believed to dedifferentiate and proliferate in response to vessel injury. Recently, adventitial progenitor cells were implicated as a source of VSMCs involved in vessel remodeling. c-Myb is a transcription factor known to regulate VSMC proliferation in vivo and differentiation of VSMCs from mouse embryonic stem cell–derived progenitors in vitro. However, the role of c-Myb in regulating specific adult vascular progenitor cell populations was not known. Our objective was to examine the role of c-Myb in the proliferation and differentiation of Sca1+ adventitial VSMC progenitor cells. Approach and Results—Using mice with wild-type or hypomorphic c-myb (c-mybh/h), BrdU (bromodeoxyuridine) uptake and flow cytometry revealed defective proliferation of Sca1+ adventitial VSMC progenitor cells at 8, 14, and 28 days post carotid artery denudation injury in c-mybh/h arteries. c-mybh/h cKit+CD34−Flk1−Sca1+CD45−Lin− cells failed to proliferate, suggesting that c-myb re...