Abstract
Pulmonary arterial hypertension (PAH) is a serious disease characterized by elevated pulmonary artery pressure, inflammatory cell infiltration and pulmonary vascular remodeling. However, little is known about the pathogenic mechanisms underlying the disease onset and progression. RNA sequencing (RNA-seq) was used to identify the transcriptional profiling in control and rats injected with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. A total of 23200 transcripts and 280, 1342, 908 and 3155 differentially expressed genes (DEGs) were identified at the end of week 1, 2, 3 and 4, of which Svop was the common top 10 DEGs over the course of PAH progression. Functional enrichment analysis of DEGs showed inflammatory/immune response occurred in the early stage of PAH development. KEGG pathway enrichment analysis of DEGs showed that cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction were in the initiation and progression of PAH. Further analysis revealed impaired expression of cholinergic receptors, adrenergic receptors including alpha1, beta1 and beta2 receptor, and dysregulated expression of γ-aminobutyric acid receptors. In summary, the dysregulated inflammation/immunity and neuroactive ligand receptor signaling pathways may be involved in the onset and progression of PAH.
Highlights
Pulmonary arterial hypertension (PAH) is a lifethreatening disease characterized by elevated pulmonary arterial pressure, infiltration of inflammatory cells and pulmonary vascular remodeling, leading to right heart failure and premature death
KEGG pathway enrichment analysis of differentially expressed genes (DEGs) showed that cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction were in the initiation and progression of PAH
Functional enrichment analysis of DEGs showed inflammatory/immune response occurred at the early time point of PAH development
Summary
Pulmonary arterial hypertension (PAH) is a lifethreatening disease characterized by elevated pulmonary arterial pressure, infiltration of inflammatory cells and pulmonary vascular remodeling, leading to right heart failure and premature death. Microarray has been used to detect transcriptional profiling in explanted lungs from various forms of advanced PAH and identified a great deal of information on PAH, including gene expression signatures, potential biomarkers and therapeutic www.aging-us.com targets [3]. Microarray has several limitations, including high background level, a limited dynamic detection range and lack of sensitivity in detecting low copy transcripts [4]. RNA-seq has emerged as an alternative to microarray, because of its accuracy, sensibility, larger dynamic detection range and higher reproducibility than microarray [4, 5]. The comparison of RNA-seq with microarray in quantifying gene expression level has been carried out in schistosoma-induced pulmonary hypertension, which showed that the correlation between microarray and RNA-seq was lower, especially for low copy transcripts where RNA-seq had a wider dynamic range than microarray [6]
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