FTI treatment begun at 9 months of age prevents the late progression of VSMC loss and proteoglycan accumulation in G608G LMNA transgenic mice. (A) Movat-stained sections of the descending aortas of four 15-month-old transgenic mice treated with 0 or 450 mg/kg/day of FTI beginning at 9 months of age (red, VSMCs; green, proteoglycan; black, elastin layers). Whereas untreated 15-month-old transgenic mice display a complete lack of VSMCs and abundant proteoglycan accumulation as well as marked adventitial thickening (black arrowhead), treated mice appear virtually identical to age-matched untreated WT controls. (B) Immunofluorescence of the sections of the descending aortas of four 15-month-old mice treated with 0 or 450 mg/kg/day of FTI (blue, DNA; green, smooth muscle α-actin; red, lamins A/C; lamin A/C appears pink due to the overlay with the blue DAPI staining; white scale bar in upper left is 20 μm). Both sets of sections demonstrate complete protection in mice beginning treatment at the late age of 9 months. Untreated vessels are almost completely devoid of any VSMCs in the media, and proteoglycan has accumulated to replace them. In contrast, FTI-treated mice appear quite similar to untreated WT control mice with the vessel media well populated by VSMCs. (C) A sampling of scatter plots depicting average pathology scores (0–5 scale) given by five blinded observers scoring Movat descending aorta, ascending aorta, carotid artery, and abdominal aorta images from G608G LMNA transgenic mice treated from 9 to 15 months of age. The trend lines demonstrate the highly significant prevention trend with increasing levels of FTI activity in all plots.