Anti-TRAIL antibody treatment of established PAH in the MCT rat model prolongs survival and reduces pulmonary vascular remodeling. (A) Kaplan-Meier plot of survival in IgG and anti-TRAIL–treated rats. (B–E) Bar graphs show RVSP (B), RVEDP (C), LVESP (D), and LVEDP (E), measured in mm Hg. (F–I) PA AT (F), cardiac index (G), ePVRi (H), and RVH (I). (J) The degree of medial wall thickness as a ratio of total vessel size (Media/CSA). (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 MCT-injected rats treated with either IgG isotype control or an anti-TRAIL antibody. 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 = 6 animals per group. *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared with IgG-treated MCT-injected rats. Arrows point to TUNEL-positive cells. Bars, 50 µm.