Figure 5.

Gene Expression Analysis (RNA-seq) of Rat Whole Lung Samples Reveals Key DEGs Likely Contributing to Beneficial Effects of TPHi Therapy

(A) Heatmap of DEGs whose differential expression was reverted by the TPHi therapy. These DEGs are likely involved in biological processes mediated by serotonin signaling and associated with pulmonary arterial hypertension (PAH); however, the roles of many of these genes remain unclear. (B) Heatmap of selected treatment DEGs (SuHx+TPHi vs SuHx) and their corresponding expression in the PAH model (SuHx vs ConNx). The selection is relevant to PAH based on the literature. (C) Proposed model of TPHi therapy based on observed gene expression (RNA-seq, no additional validation) indicates likely beneficial effects, ie, decrease in: 1) vasoconstriction; 2) pulmonary arterial smooth muscle cell (PASMC) proliferation; 3) vascular fibrosis; and 4) inflammation. Targets indicated in bold were significantly differentially expressed (false discovery rate <0.05 and fold changes >2 or <0.5). The arrows next to targets indicate the observed up-regulation (↑) or down-regulation (↓). The arrows and T-bars in the models indicate the effects (induction or suppression, respectively) known from the literature. The arrows next to biological processes (↑ or ↓) follow from the observed regulation of the upstream targets. Sample sizes: ConNx, n = 4; SuHx, n = 6; SuHx+TPHi, n = 4. 5-HT = 5-hydroxytryptamine (serotonin); cGMP = cyclic guanosine monophosphate; ConNx = control group in normoxia; Hx = hypoxia; NO = nitric oxide; PKG = protein kinase G; ROS = reactive oxygen species; SuHx = Sugen 5416 in hypoxia; TPH, tryptophan hydroxylase.