ArticleAmerican journal of respiratory cell and molecular biology2019
Hypoxia-induced Pulmonary Hypertension in Different Mouse Strains: Relation to Transcriptome.
Article in American journal of respiratory cell and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- A Cross-Species and Sex-Specific Meta-Analysis of Transcriptomic Studies of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Pooled it
- Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension.Journal of translational medicine · 2025Review
- Molecular Diplomacy of Lipids in the War of Immunity: Bridging Rare and Common Disease Mechanisms.International journal of molecular sciences · 2025Article
- MicroRNA-210 mediates hypoxia-induced pulmonary hypertension by targeting mitochondrial bioenergetics and mtROS flux.Acta physiologica (Oxford, England) · 2024Article
- Crocin's role in modulating MMP2/TIMP1 and mitigating hypoxia-induced pulmonary hypertension in mice.Scientific reports · 2024Article
- Polo-like kinase 1 promotes pulmonary hypertension.Respiratory research · 2023Article
- Intrapulmonary arterial contraction assay reveals region-specific deregulation of vasoreactivity to lung injuries.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension.Life science alliance · 2022Article
- Article
- Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation.International immunopharmacology · 2022Review
- Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature.Journal of vascular research · 2022Article
- Review
- Apelin/APJ system: an emerging therapeutic target for respiratory diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Update in Pulmonary Vascular Diseases and Right Ventricular Dysfunction 2019.American journal of respiratory and critical care medicine · 2020Article
- Analysis of lncRNA-miRNA-mRNA Interactions in Hyper-proliferative Human Pulmonary Arterial Smooth Muscle Cells.Scientific reports · 2019Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Patients with pulmonary arterial hypertension (PAH) can harbor mutations in several genes, most commonly in BMPR2. However, disease penetrance in patients with BMPR2 mutations is low. In addition, most patients do not carry known PAH gene mutations, suggesting that other factors determine susceptibility to PAH. To begin to identify additional genomic factors contributing to PAH pathogenesis, we exposed 32 mouse strains to chronic hypoxia. We found that the PL/J strain has extremely high right ventricular systolic pressure (RVSP; 86.58 mm Hg) but minimal lung remodeling. To identify potential genomic factors contributing to the high RVSP, RNAseq analysis of PL/J lung mRNAs and microRNAs (miRNAs) after hypoxia was performed, and it demonstrated that 4 of 43 upregulated miRNAs in the Dlk1-Dio3 imprinting region are predicted to target T cell marker mRNAs. These target mRNAs, as well as the numbers of T cells were downregulated. In addition, C5a and its receptor, C5AR1, were increased. Analysis of Rho-associated protein kinase (Rock) 2 mRNA expression, in the RhoA/Rock pathway, demonstrated a significant increase in PL/J. Inhibition of Rock2 ameliorated a portion of the elevated RVSP. In addition, we identified miR-150-5p as a potential regulator of Rock2 expression. In conclusion, we identified two possible pathways contributing to the hypoxia pulmonary hypertension phenotype of extreme RVSP elevation: aberrant T cell expression driven by hypoxia-induced miRNAs and increased expression of C5a and C5AR1. We suggest that the PL/J mouse will be a good model for seeking mechanism(s) of RVSP elevation in hypoxia-induced PAH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.