Three weeks of SMC CYB5R3 knockdown increases mPAP and RV end diastolic pressure in SS chimeras. Chimeras testing 80% or greater engraftment, assessed by Hb electrophoresis, were aged an additional 3 weeks (A-F) or 12 weeks (G-L) on regular diet before measurement of hemodynamics by RV microcatheterization. RV contractile index (A), mPAP (B), RV end diastolic pressure (C), RV maximum pressure rise (dP/dT max) (D), τ Weiss (W) (E), and RV minimum pressure rise (dP/dT min) (F) for SS/R3^KD (blue bar) and SS/R3^WT chimeras (red bar) for the 3-week study. RV contractile index (G), mPAP (H), RV end diastolic pressure (I), RV dP/dT max (J), τ Weiss (W) (K), and RV dP/dT min (L) for SS/R3^KD (blue bar) and SS/R3^WT chimeras (red bar) in the 12-week study. RV Contractile Index was not affected by 3- (A) or 12-week (G) knockdown of CYB5R3 in smooth muscle. Differences between the mPAP (B) and RV end diastolic pressure (C) that had been apparent at 3-week knockdown of CYB5R3 in smooth muscle was no longer apparent at 12-week knockdown (panels H and I, respectively). The mean ± SEM is represented. A nonparametric Mann-Whitney U test was used to determine statistical significance when F test indicated a non-Gaussian distribution of variance between groups.