Role of Stem Cell Antigen-1 in Vessel Remodeling

Vessel remodeling underlies several vascular diseases and involves the expansion and differentiation of stem cell antigen-1 (Sca-1)-expressing progenitor cells into vascular smooth muscle cells and related myofibroblast-like cells. Although used to identify progenitor cells, the functional role of Sca-1 has not been examined in vascular remodeling. Here, we first identified the dynamics of Sca-1 expression in a wire injury model of vessel remodeling. To determine the requirement for Sca-1, mice deficient in Sca-1 (Sca1KO) and wild-type controls underwent carotid wire injury. Sca1KO displayed more intimal and adventitial remodeling post-injury. At 8d, non-leukocyte proliferation was increased throughout the vessel, and confined to the adventitia at 14d post-injury. Minimal differences in endothelial- and smooth muscle cells were observed, but fibroblasts and leukocytes were significantly increased, suggesting disinhibited pro-fibrotic and pro-inflammatory responses to injury. Our findings suggest that Sca-1 expression protects against vessel remodeling by suppressing fibrotic and inflammatory responses to injury.M.Sc