Anti-TRAIL antibody treatment of established PAH in the Paigen diet–fed ApoE^−/− mouse induces disease regression. (A–D) Bar graphs show RVSP (A), RVEDP (B), LVESP (C), and LVEDP (D), measured in mm Hg. (E–H) PA AT (E), cardiac index (F), ePVRi (G), and RVH (H). (I) The degree of medial wall thickness as a ratio of total vessel size (Media/CSA). (J) Relative percentage of muscularized small pulmonary arteries and arterioles in <50 µm vessels. (K and L) Quantification of the percentage of proliferating cells (PCNA positive; K) and apoptotic (TUNEL positive; L) separated into pulmonary arteries <50 µm in diameter, vessels from 51 to 100 µm in diameter, and vessels >100 µm in diameter. (M) Representative photomicrographs of serial lung sections from ApoE^−/− mice fed on Paigen diet for 12 wk. Sections were stained with Alcian Blue Elastic van Gieson (ABEVG) or immunostained for α-SMA, PCNA, or TUNEL. (N) Representative confocal microscopy image showing apoptotic cells (green) and SMC (red) with dual-positive cells (yellow) highlighted by white arrows. Error bars represent mean ± SEM, n = 4–6 animals per group. *, P < 0.05; **, P < 0.01, compared with IgG-treated Paigen diet-fed mice. Arrows point to TUNEL-positive cells. Bars, 50 µm.