Figure 8.

Normal vascular phenotype and lifespan in HGPSrev-SM22α-Cre mice with progerin suppression and lamin A restoration restricted to vascular smooth muscle cells (VSMCs) and cardiomyocytes. A, Representative immunofluorescence images of thoracic aorta and hearts of ≈13-month-old mice. Cross-sections were costained with antibodies against CD31 (green), smooth muscle α-actin (SMA; red) and progerin (white) and with Hoechst 33342 (blue) to visualize endothelial cells, vascular smooth muscle cells (VSMCs), progerin, and nuclei, respectively. B, Western blot of lamin A/C, progerin, and GAPDH in tissues of ≈13-month-old mice. C, Body weight curves (n=9 WT; n=13 HGPSrev; n=11 HGPSrev-SM22α-Cre). Differences were analyzed by unpaired multiple t tests and the Holm-Sídák correction. Red asterisks denote differences between HGPSrev-SM22α-Cre and HGPSrev mice. Black asterisks denote differences between HGPSrev-SM22α-Cre and WT mice. D, Kaplan-Meier survival curve (n=15 WT; n=15 HGPSrev; n=11 HGPSrev-SM22α-Cre). Median lifespan was 13.73 months in HGPSrev mice, 22.4 months in HGPSrev-SM22α-Cre mice, and 22.97 months in WT mice. Differences were analyzed with the Mantel-Cox test. E and F, Representative images of aortic arch stained with hematoxylin-eosin (H&E) and Masson’s trichrome, to quantify VSMCs and fibrosis, respectively, in ≈13-month-old WT mice (n=6), HGPSrev mice (n=5 or 6), and HGPSrev-SM22α-Cre mice (n=5). Differences were analyzed by 1-way ANOVA with the post hoc Tukey test. *P<0.05; ****P<0.0001. Each symbol represents 1 animal. Data are mean±SEM. A indicates adventitia; L, lumen; and M, media. Scale bars, 25 µm (except in the tile scans in A, where they are 200 µm).