Figure 1

Vascular fibrosis in transgenic mice is associated with increased TGF-β expression and signaling. H&E, Masson trichrome, and picrosirius red (viewed under polarized light) staining of wild-type and transgenic thoracic aorta sections (a-c). Smooth muscle layer architecture, elastic fibers, and smooth muscle layer are normal in the transgenic animals. However, adventitial collagen content is increased, and fibers are thicker in the transgenic animals on Masson trichrome and sirius red staining. LAP(TGF-β1) and free TGF-β1 expression is increased particularly in the adventitia (arrows) but also in smooth muscle cells (d-f). Immunostaining for pSmad2/3 confirms increased nuclear translocation in the transgenic compared with the wild-type. Original magnification, ×20; representative images for panels (a-f) from transgenic (n = 6) and wild-type (n = 6) littermate sex-matched controls. (g) Serial measurements of adventitial and smooth muscle thickness show transgenic adventitial thickening and smooth muscle layer attenuation; summary data are expressed as mean ± SEM. *P < 0.05, from transgenic (n = 6) and wild-type (n = 6) littermate sex-matched controls. (h) Summary data from measurement of non-crosslinked collagen concentration compared with collagen standards (Sircol assay) show significantly higher collagen in transgenic animals compared with wild-type. Data are expressed as mean ± SEM.*P < 0.05, from transgenic (n = 8) and wild-type (n = 8) littermate sex-matched controls.