Figure 4.
Effect of Sirt3 deletion on chronic hypoxia–induced pulmonary hypertension. (A–F) Sirt3+/+ or Sirt3−/− mice housed under normoxic (room air; Normoxia) or hypoxic (10% O2; Hypoxia) conditions for 30 days. (A) Chronic hypoxia decreased pulmonary acceleration time (PAT)/ejection time (ET) in Sirt3−/− mice, but this response was not different from that in Sirt3+/+ animals. (B) Chronic hypoxia increased right ventricular (RV) systolic pressure (RVSP) in Sirt3−/− mice, but this response was not different from that in Sirt3+/+ animals. (C) Chronic hypoxia increased the acute hypoxia (5% O2; 1-min ventilation)–induced change in RVSP in Sirt3−/− mice, but this response was not different from that in Sirt3+/+ animals. (D) Inflation-fixed, hematoxylin and eosin–stained lung sections demonstrate chronic hypoxia–induced vascular remodeling. “PA” denotes small PAs. Left image denotes a lung section from a Normoxia Sirt3+/+ mouse; right image is from a Hypoxia Sirt3+/+ mouse. (E) Chronic hypoxia–induced vascular remodeling as assessed by PA wall thickness in both Sirt3+/+ and Sirt3−/− mice compared with their normoxic counterparts. (F) Chronic hypoxia–induced RV hypertrophy as assessed by the Fulton index in both Sirt3+/+ and Sirt3−/− mice compared with their normoxic counterparts. Values are means (± SEM); n = 6–10 mice per experimental group. *P < 0.05 compared with Normoxia Sirt3+/+ mice; †P < 0.05 compared with Normoxia Sirt3−/− mice. LV, left ventricular; S, septum.