Molecular Profiling of Vascular Remodeling in Chronic Pulmonary Disease

Borchert, Paul; Stark, Helge; Hoefer, Anne; Vogel‐Claussen, Jens; Warnecke, G.; Eubel, Holger; Kuenzler, Patrick; Kreipe, Hans-Heinrich; Hoeper, Marius M.; Jonigk, Danny

doi:10.1016/j.ajpath.2020.03.008

Cited by 18 publications

(10 citation statements)

References 37 publications

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“…More studies are warranted to confirm the role of G6PD in the disease setting. In line with our findings, the study by Neubert et al (2020 ) showed a decreased expression of FGR in pulmonary veno-occlusive disease (PAH with overt features of venous/capillary involvement) lung explants compared to that of healthy control samples. Li et al (2020 ) conducted a comprehensive miRNA–mRNA network analysis and identified that AQP9 was one of the five hub genes possibly involved in the pathogenesis of idiopathic PAH.…”

Section: Discussionsupporting

confidence: 91%

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension

et al. 2022

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Objective: Regulatory T cells (Tregs) are critical immune modulators to maintain immune homeostasis and limit pulmonary hypertension (PH). This study was aimed to identify Treg-related genes (TRGs) in PH.Methods: The gene expression profile from lungs of PH patients was retrieved from the Gene Expression Omnibus (GEO) database. The abundance of Tregs was estimated by the xCell algorithm, the correlation of which with differentially expressed genes (DEGs) was performed. DEGs with a |Pearson correlation coefficient| >0.4 were identified as TRGs. Functional annotation and the protein–protein interaction (PPI) network were analyzed. A gene signature for 25 hub TRGs (TRGscore) was generated by a single sample scoring method to determine its accuracy to distinguish PH from control subjects. TRGs were validated in datasets of transcriptional profiling of PH cohorts and in lung tissues of experimental PH mice.Results: A total of 819 DEGs were identified in lungs of 58 PAH patients compared to that of 25 control subjects of dataset GSE117261. In total, 165 of all these DEGs were correlated with the abundance of Tregs and identified as TRGs, with 90 upregulated genes and 75 downregulated genes compared to that of control subjects. The upregulated TRGs were enriched in negative regulation of multiple pathways, such as cAMP-mediated signaling and I-kappaB kinase/NF-kappaB signaling, and regulated by multiple genes encoding transcriptional factors including HIF1A. Furthermore, 25 hub genes categorized into three clusters out of 165 TRGs were derived, and we identified 27 potential drugs targeting 10 hub TRGs. The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7). Among them, 10 genes including NCF2, MNDA/Ifi211, HCK, FGR, CSF3R, AQP9, S100A8, G6PD/G6pdx, PGD, and TXNRD1 were significantly reduced in lungs of severe PH patients of dataset GSE24988 as well as in lungs of hypoxic PH mice compared to corresponding controls.Conclusion: Our finding will shed some light on the Treg-associated therapeutic targets in the progression of PH and emphasize on TRGscore as a novel indicator for PH.

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Section: Discussionsupporting

confidence: 91%

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension

et al. 2022

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“…VEGFA and related signaling pathways play a critical role in the development of COPD through the inflammatory response and vascular remodelling based on the maintenance of endothelial and epithelial cell viability (Westergren- Thorsson et al, 2018). Since the central airways undergo bronchial vascular remodelling and the bronchial vascular area and vessel size are increased, COPD occurs (Neubert et al, 2020). Higher bronchial expressions of VEGF, basic fibroblast growth factor and transforming growth factor β (TGF-β)…”

Section: Discussionmentioning

confidence: 99%

Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations

Gao

Wang

Jiao

et al. 2021

Experimental Physiology

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We attempted to define the associations between single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene and chronic obstructive pulmonary disease (COPD) in Chinese Han and Mongolian cohorts. Five SNPs were genotyped in cohorts of 684 COPD patients (350 Mongolian and 334 Han) and 784 healthy controls (350 Mongolian and 434 Han) using SNPscan multiplex PCR. SNP frequencies, genetic models and haplotypes were analysed using the chi-square test.The associations of SNPs with COPD and linkage disequilibrium were analysed using logistic regression and HaploView, respectively. We found that only rs833068G>A, rs833070T>C and rs3024997G>A were significantly associated with the risk of COPD in the Mongolian population (rs833068: P < 0.

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“…PCH was previously thought to occur only in conjunction with PVOD, but has recently been shown to also occur independently. As in P(A)H, pulmonary haemorrhage of varying extent with haemosiderin-laden macrophages is frequent in PVOD/ PCH (supplementary figure S7) [97]. Pulmonary venous hypertension may not only manifest in PVOD, but also occurs with pulmonary vein stenosis or left ventricular heart failure.…”

Section: Ild With Structural Vascular Changes (B4)mentioning

confidence: 90%

“…Nevertheless, lung biopsies can be of substantial value to differentiate PAH from pulmonary veno-occlusive disease (PVOD), which show substantial overlap in haemodynamic findings [97]. Depending on the severity and temporal evolvement of PAH, histomorphological features range from medial and intimal hyperplasia, (sub)total fibrotic luminary occlusion, referred to as concentric lesions, dilatation lesions and formation of plexiform lesions (complex, glomeruloid-like vascular structures) to necrotising arteritis.…”

Section: Ild With Structural Vascular Changes (B4)mentioning

confidence: 99%

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Interstitial lung disease in infancy and early childhood: a clinicopathological primer

et al. 2022

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Children's interstitial lung disease (chILD) encompasses a wide and heterogeneous spectrum of diseases substantially different from that of adults. Established classification systems divide chILD into conditions more prevalent in infancy and other conditions occurring at any age. This categorisation is based on a multidisciplinary approach including clinical, radiological, genetic and histological findings. The diagnostic evaluation may include lung biopsies if other diagnostic approaches failed to identify a precise chILD entity, or if severe or refractory respiratory distress of unknown cause is present. As the majority of children will be evaluated and diagnosed outside of specialist centres, this review summarises relevant clinical, genetic and histological findings of chILD to provide assistance in clinical assessment and rational diagnostics.

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Molecular Profiling of Vascular Remodeling in Chronic Pulmonary Disease

Cited by 18 publications

References 37 publications

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension

Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations

Interstitial lung disease in infancy and early childhood: a clinicopathological primer

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