Identification of the Key Pathways and Genes in Hypoxia Pulmonary Arterial Hypertension Following Intrauterine Growth Retardation

Weifen Zhu, Ziming Zhang, Weiwei Gui, Zheng Shen, Yixin Chen, Xueyao Yin, Li Liang, Lin Li
The Affiliated Sir Run Run Shaw Hospital, Children’s Hospital and The First Affiliated Hospital of Zhejiang University.
China

Frontiers in Molecular Biosciences
Front Mol Biosci 2022;
DOI: 10.3389/fmolb.2022.789736

Abstract
High-throughput sequencing and weighted gene co-expression network analysis (WGCNA) were used to identify susceptibility modules and genes in liver tissue for the hypoxic pulmonary arterial hypertension (PAH) animal model following intrauterine growth retardation (IUGR). A total of 5,000 genes were clustered into eight co-expression modules via WGCNA. Module blue was mostly significantly correlated with the IUGR-hypoxia group. Gene Ontology analysis showed that genes in the module blue were mainly enriched in the fatty acid metabolic process, lipid modification, and fatty acid catabolic process. The Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes in module blue were mainly associated with fatty acid metabolism, PPAR signaling pathway, and biosynthesis of unsaturated fatty acids. In addition, the maximal clique centrality method was used to identify the hub genes in the subnetworks, and the obtained results were verified using real-time quantitative PCR. Finally, we identified that four genes including Cyp2f4, Lipc, Acadl, and Hacl1 were significantly associated with IUGR-hypoxia. Our study identified a module and several key genes that acted as essential components in the etiology of the long-term metabolic consequences in hypoxia PAH following IUGR.

Category
Animal Models of Pulmonary Vascular Disease and Therapy
Genetic Factors Associated with Pulmonary Vascular Disease
Environmental Factors Associated with Pulmonary Vascular Disease
Class I. Persistent Pulmonary Hypertension of the Newborn
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia

Age Focus: Pediatric Pulmonary Vascular Disease

Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication

Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes

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