Figure 9. Senolytic therapy prevents FXN-dependent PH development.

(A) Diagram for senolytic treatment in female and male hypoxic EC Fxn^–/– mice. ABT-263 (25 mg/kg/day) or vehicle control (n = 5/group) was administered via oral gavage in weeks 2 and 3 of hypoxic exposure (3 weeks, 10% O₂). (B) Immunofluorescence staining and assessment of Cd11b⁺ myeloid cells (orange), α-SMA⁺ vessel smooth muscle cells (green), and counterstaining of nuclei (blue). (C) Representative confocal images and quantified percentage of pulmonary vessel muscularization by immunofluorescence staining of vWF (green) and α-SMA (red). (D) RVSP (mmHg). (E) Diagram depicting senolytic treatment in female and male IL-6 Tg mice during weeks 2 and 3 of hypoxic exposure. (F) Measurement of vessel-associated inflammatory infiltration via Cd11b (orange) (n = 5 versus n = 4). (G) Representative images and quantified percentage of vessel muscularization measured by immunofluorescence staining of vWF (green) and α-SMA (red) (n = 3/group). (H) RVSP (n = 4 versus n = 3). (I) Fulton index (RV/LV+S, %) (n = 5 versus n = 4). (J) Diagram of male hypoxic WT mice treated with ABT-263 (n = 5/group). (K) Vessel-associated CD11b⁺ cells. (L) RVSP. Two-tailed Student’s t test was performed with error bars that reflect mean ± SD. Scale bars: 50 μm.