Crucial role of the stromal cell derived factor-la (SDF-1a)/CXCR4 axis in smooth muscle cell (SMC) progenitor recruitment after arterial injury

摘要

Recent evidence has inferred a role of SDF-la in neointimal hyperplasia and recruitment of circulating progenitor cells after arterial injury. We show that treatment of atherosclerosisprone apoE"/_ mice transplanted, with LacZ+ bone marrow with a neutralizing SDF-la mAb for 4 weeks indeed reduced neointimal plaque area after wire-injury of the carotid artery, and was associated with a decrease in bone marrow-derived SMC content. Similarly, repopulation of apoE7" mice with bone marrow deficient in the SDF-la receptor CXCR4 diminished wireinduced neointimal hyperplasia and SMC content. One day after wire-injury of apoE_/" carotid arteries, SDF-la is expressed in medial SMCs concomitant with apoptosis and mediates the in situ recruitment of progenitor cells in arteries perfused ex vivo. Knocking-down local SDF-la induction by lentiviral transduction of carotid arteries with siRNA inhibited neointimal hyperplasia after 4 weeks. These data demonstrate that SDF-la and its receptor CXCR4 play an instrumental role in the recruitment of bone marrow-derived SMC progenitor cells to neointimal lesions, thereby contributing to neointimal hyperplasia after vascular injury. The involvement of local SDF-la may be targeted to limit excessive repair after vascular injury.