Figure 6

Rosiglitazone (RSG) treatment reduces neointimal hyperplasia after vascular injury in rat carotid artery by modulating vascular smooth muscle cell (VSMC) phenotype. (a) Representative images of the vessels at 2 weeks after injury. RSG treatment significantly reduced neointimal hyperplasia compared with the balloon-injury-alone group. A, adventitia; I, intima; M, media; scale bar=100 μm (upper panel) and 20 μm (lower panel). (b) Quantification graphs of I/M ratio at 2 weeks after injury. This graph shows a markedly reduced I/M ratio in the RSG-treated group (n=10). *P<0.05 vs balloon injury group. (c, d) Immunohistochemical staining for terminal deoxynucleotidyl transferase (TdT)–mediated dUTP nick end labeling (TUNEL) or proliferating cell nuclear antigen (PCNA) expression in the carotid artery wall. Compared with the balloon injury group, RSG treatment decreased VSMC proliferation (PCNA positive) and increased VSMC apoptosis (TUNEL positive). Scale bar=20 μm. (e–g) Immunohistochemical staining for calponin, α-smooth muscle actin (SMA) and thrombospondin. (e, f) Compared with the intact arteries before balloon injury, the injured arteries showed decreased calponin and α-SMA (markers of contractile form), which was reversed by RSG treatment. Scale bar=20 μm. (g) For thrombospondin (a marker of synthetic form), RSG had the opposite effect. These results suggest that RSG could prevent neointimal hyperplasia by modulating VSMC phenotype even in vivo.