Figure 5. Townes sickle mice display right ventricular dysfunction but no in vivo thrombosis or pulmonary arterial hypertension.

(A) Representative histological sections of liver and lung from hypoxia/reoxygenation-treated AA, SS, and SSCKO mice. (Top panel) Extensive focal hepatic necrosis with chronic inflammation in the livers of SS and SSCKO mice without visible fibrin thrombi. (Bottom panel) Normal lung histology in SS and SSCKO compared to WT mice exposed to hypoxia/reoxygenation treatment. Images were taken on an Olympus BX45 microscope with 20×/0.50 numerical aperture UPlanFl objective or 40×/0.75 NA UPlanFl objective, and using Infinity II camera and Infinity Capture software. H&E stained sections were captured at 20× (lung) and 10× (liver) magnification. (B) Right ventricular hypertrophy is present in SS (***P < 0.00001 vs. WT mice, n = 6 – 8 mice per genotype, unpaired t test) and SSCKO mice (** P < 0.01 vs. WT mice, n = 6 – 7 mice per genotype, unpaired t test). (C) Similarly, left ventricular hypertrophy is present in SS (***P < 0.001 vs. WT mice, n = 6 – 8 mice per genotype, unpaired t test) and SSCKO mice (** P < 0.01) vs. WT mice, n = 6 – 7 mice per genotype, unpaired t test). (D) The Fulton ratio of ventricular weights (right ventricle-left ventricle including septum) [63] is normal in SS and SSCKO compared to WT mice. By exhibiting hypertrophy in both left and right ventricles, the SS and SSCKO have a similar Fulton ratio compared to WT mice. (E) Right ventricular systolic pressure (RVSP), the key indicator of pulmonary arterial hypertension (PAH) in lungs was measured in steady state and H/R-treated C57BL/6 wild type (WT), SS, and SSCKO mice. RSVP values are not elevated in Townes SS and SSCKO mice as compared to their wild type counterparts. Data are shown as mean ± SEM of 3 – 6 mice per genotype. * P < 0.05.