Human activin-A is expressed in the atherosclerotic lesion and promotes the contractile phenotype of smooth muscle cells

Activin is a member of the transforming growth factor-beta superfamily, and it modulates the proliferation and differentiation of various target cells . In this study, we investigated the role of activin in the initiation and progression of human atherosclerosis. The expression of activin, its physio logical inhibitor follistatin, and activin receptors were assayed in human vascular tissue specimens that represented Various stages of atherogenesis. In situ hybridization experiments revealed activin mRNA in endothelial cel ls and macrophages and a strong induction of activin expression in neointim al smooth muscle cells from the early onset of atherogenesis. We developed an "in situ free-activin binding assay" by using biotinylated follistatin, which allowed us to detect bioactive activin at specific sites in atheroscl erotic lesions. The mRNAs encoding the activin receptors are expressed simi larly in normal and atherosclerotic tissue, which indicates that activin-A signaling in atherogenesis is most likely dependent on changes in growth fa ctor concentrations rather than on receptor levels. In vitro, activin induc es the contractile, nonproliferative phenotype in cultured smooth muscle ce lls, as is reflected by increased expression of smooth muscle-specific mark ers (SM alpha-actin End SM22 alpha). Our data provide evidence that activin induces redifferentiation of neointimal smooth muscle cells, and we hypoth esize that activin is involved in plaque stabilization.