Background
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, with complex etiology, difficult treatment and poor prognosis. The objective of this study was to investigate the potential biomarkers for PAH based on bioinformatics analysis.
Methods
The GSE117261 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by screening PAH patients and controls. Then the DEGs were analyzed using a Weighted Gene Co-expression Network Analysis (WGCNA) and the key modules were determined, and to further explore their potential biological functions via Gene Ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes Pathway analysis (KEGG), and Gene Set Enrichment Analysis (GSEA). Moreover, Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates in the key modules. Finally, real-time quantitative polymerase chain reaction was supplied to detect the expressions of hub genes in human pulmonary arterial smooth cells treated with cobalt chloride (COCl2) which was used to mimic hypoxia.
Results
There were 2299 DEGs identified. WGCNA indicated that yellow module was the key one correlated with PAH. GO and KEGG analysis demonstrated that genes in the yellow module were mainly enriched in ‘Pathways in cancer’. GSEA revealed that ‘HALLMARK_MYC_TARGETS_V1’ was remarkably enriched in PAH. Based on the PPI network, vascular endothelial growth factor A, proto-oncogene receptor tyrosine kinase (KIT), PNN interacting serine and arginine rich protein (PNISR) and heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) were identified as the hub genes. Additionally, the PCR indicated that the elevated expressions of PNISR and HNRNPH1 were in line with the bioinformatics analysis. ROC analysis determined that PNISR and HNRNPH1 may be potential biomarkers to provide better diagnosis of PAH.
Conclusion
PNISR and HNRNPH1 were potential biomarkers to diagnosis PAH. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of PAH.
Obesity and overweight are closely related to cardiovascular mortality. Arterial stiffness is one of the important risks for cardiovascular diseases and is strongly related with the cardiovascular mortality. However, the relationship between obesity and arterial stiffness is still controversial. A cross-sectional study was performed to examine the relationship of body fat percentage (BFP), an indicator of obesity, with carotidfemoral pulse wave velocity (cfPWV) in 2603 subjects (aged 58.62 ± 11.27 years, male 71.07%, hypertension 64.89%). All participants were divided into four groups according to the gender and the presence of arterial stiffening based on a value ≥10 m/s of cfPWV(group1 : male with cfPWV <10 m/s, group2 : male with cfPWV ≥10 m/s, group3 : female with cfPWV <10 m/s, group4 : female with cfPWV ≥10 m/s). Body weight, height, waist circumference, blood pressure were measured and clinical biochemical tests were recorded. cfPWV was measured using a non-invasive automatic device (Complior Analysis, France). BFP were calculated by CUN-BAE equation. The level of cfPWV was significantly increased with the increasing trend of BFP in both males and females. Stepwise multiple regression analysis revealed that SBP, DBP, HR, Hcy, BFP, FPG were independent associated with cfPWV in females and SBP, eGFR, FPG, BFP, DBP were independent associated with cfPWV in males. In the subgroups stratified by age, BFP was correlated with cfPWV only in females over 60 years old, but not in female those aged under 60 years old and males. In addition to the age and blood pressure, BFP was one of important predictor of arterial stiffening special in females aged over 60 years old.
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