Figure 3. Inhibition of excessive PKCβ or ERK signaling prevents death due to aortic dissection.

(A) Kaplan-Meier survival curve comparing Col3a1^G938D/+ (n = 93) to Col3a1^G938D/+ (n = 16) mice receiving ruboxistaurin in the diet starting at weaning and continuing for 40 days. Significant differences were calculated using log-rank (Mantel-Cox) analysis. P21 = postnatal day 21. (B) Representative Western blot and analysis of pPKCβ and pERK comparing Col3a1^+/+ (n = 6) to Col3a1^G938D/+ (n = 6) proximal descending aortas and quantification of pPKCβ and pERK levels normalized to β-actin loading control for vEDS aortas. Error bars show mean ± SEM. Asterisks signify significant differences using 1-way ANOVA with Dunnett’s multiple comparisons post hoc test. **P < 0.01, ***P < 0.001, DF = 3, F = 13. (C) Kaplan-Meier survival curve comparing Col3a1^G938D/+ (n = 93) to Col3a1^G938D/+ (n = 20) mice receiving cobimetinib in the drinking water starting at weaning and continuing for 40 days. Significant differences were calculated using log-rank (Mantel-Cox) analysis. P21 = postnatal day 21. All findings from drug trials are based on analyses using a universal control group with n = 93 across all drug tests that started at P21. FDR-adjusted P values are presented in Supplemental Table 3.