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. 2021 May 29;10(12):e019091. doi: 10.1161/JAHA.120.019091

Figure 4. Simultaneous pharmacologic inhibition of GLS1 and YAP1/TAZ in monocrotaline‐exposed rats modulates YAP1‐specific gene expression and glutaminase activity in the lungs.

Figure 4

(A) Study design is shown for the induction of PH using monocrotaline via intraperitoneal injection followed by administration of microparticles orotracheally for treatments. (B–D) As assessed by reverse transcriptase–quantitative polymerase chain reaction of rat lung, YAP1‐dependent gene transcripts for CTGF (B), ANKRD1 (C), and CYR61 (D) were downregulated modestly by PLGA‐encapsulated CB‐839 and more robustly by inhaled PLGA‐encapsulated verteporfin. (E) As assessed by glutaminase activity assay of rat lung, glutaminase activity was robustly downregulated by inhaled PLGA‐encapsulated CB‐839 but not verteporfin alone. In all images, mean expression in untreated groups was assigned a fold change of 1, to which relevant samples were compared. In each group, n=3 (untreated), n=5 (blank microparticles), n=3 (saline), n=5 (verteporfin), n=5 (CB‐839), and n=6 (CB839+verteporfin). Error bars represent mean±SEM. By 1‐way ANOVA and post hoc Bonferroni testing, significantly different values are represented by *<0.05, *<0.01, ***<0.001, and ****<0.00001. ANKRD1 indicates ankyrin repeat domain 1; CTGF, connective tissue growth factor; CYR61, cysteine‐rich angiogenic inducer 61; GLS1, glutaminase 1; MCT, monocrotaline; PLGA, poly(lactic‐co‐glycolic) acid; TAZ, transcriptional coactivator with PDZ‐binding motif; and YAP1, yes‐associated protein 1.