Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases

Abstract

Pulmonary arterial hypertension (PAH) is a severe cardiovascular disorder with high mortality. Multiple clinical diseases can induce PAH, but the underlying molecular mechanisms shared in PAHs associated with different diseases remain unclear. The aim of this study is to explore the key candidate genes and pathways in PAH associated with congenital heart disease (CHD-PAH), PAH associated with connective tissue disease (CTD-PAH), and idiopathic PAH (IPAH). We performed differential expression analysis based on a public microarray dataset GSE113439 and identified 1,442 differentially expressed genes, of which 80.3% were upregulated. Subsequently, both pathway enrichment analysis and protein–protein interaction network analysis revealed that the “Cell cycle” and “DNA damage” processes were significantly enriched in PAH. The expression of seven upregulated candidate genes (EIF2AK2, TOPBP1, CDC5L, DHX15, and CUL1–3) and three downregulated candidate genes (DLL4, EGFL7, and ACE) were validated by qRT-PCR. Furthermore, cell cycle-related genes Cul1 and Cul2 were identified in pulmonary arterial endothelial cells (PAECs) in vitro. The result revealed an increased expression of Cul2 in PAECs after hypoxic treatment. Silencing Cul2 could inhibit overproliferation and migration of PAECs in hypoxia. Taken together, according to bioinformatic analyses, our work revealed that “Cell cycle” and “DNA damage” process-related genes and pathways were significantly dysregulated expressed in PAHs associated with three different diseases. This commonality in molecular discovery might broaden the genetic perspective and understanding of PAH. Besides, silencing Cul2 showed a protective effect in PAECs in hypoxia. The results may provide new treatment targets in multiple diseases induced by PAH.

Bioinformatic analysis of dysregulated circular RNAs in pediatric pulmonary hypertension linked congenital heart disease

“…The common molecular mechanisms that are evident in PAH are also reflected in its genetic etiology. In turn, identically variant gene expression was found across patients with CHD-PAH, connective tissue disease PAH, and IPAH (35). Further, in our present study, hsa_circ_005372 and hsa_circ_003416 were significantly dysregulated and may play a role in regulating the expression of both host genes and downstream target genes.…”

A Case Report of Postpartum Idiopathic Pulmonary Arterial Hypertension

“…Due to the unclear etiology, the patient was ultimately diagnosed with IPAH. Nevertheless, IPAH exhibits intricate pathogenesis and individuals afflicted with IPAH commonly experience an unfavorable prognosis (12,13). The clinical management of IPAH primarily encompasses general treatment, symptomatic treatment, and targeted therapy.…”

Landscape of RNA-binding proteins in diagnostic utility, immune cell infiltration and PANoptosis features of heart failure

“…DDX52 is a type of DEAD/H box RNA helicase, and its suppression exerts an anti-tumor effect (Yu et al, 2021). The DEAH-box RNA helicase DHX15 has been identified as a potential gene for pathological cardiac hypertrophy triggered by excessive exercise (Zhou et al, 2020) and pulmonary arterial hypertension (Wang et al, 2021). EBNA1BP2 functions as a dynamic scaffold for ribosome biogenesis (Hirano et al, 2009).…”