ArticleAmerican journal of respiratory and critical care medicine2016
Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Acute pulmonary vasoreactivity: a simple test revisited in the contemporary era - a narrative review.International journal of cardiology. Heart & vasculature · 2026Review
- My Quest for Calcium Channel Blockers as the First Medical Treatment for Patients With Pulmonary Hypertension.Pulmonary circulation · 2025Article
- Mas1 Receptor Activation is Necessary and Sufficient to Transduce ACE2 Effect in PAH, But Ang(1-7) Alone is Insufficient.Pulmonary circulation · 2025Article
- Identification of a PANoptosis-related gene signature reveals therapeutic potential of SFRP2 in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Article
- A Rare Case of Polymicrogyria in an Elderly Individual With Unique Polygenic Underlining.Cureus · 2024Article
- Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update.Biomolecules · 2024Review
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Differential drug response in pulmonary arterial hypertension: The potential for precision medicine.Pulmonary circulation · 2023Review
- Association Between Circulating CD4Journal of cardiovascular translational research · 2023Article
- Case report: Pathological differences in pulmonary arterial hypertension in long-term responders to calcium channel blockers.Frontiers in cardiovascular medicine · 2023Article
- Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2023Article
- Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2022Article
- The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as aJournal of clinical medicine · 2022Article
- Promises and Pitfalls of Multiomics Approaches to Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2022Article
- Prime Time for Proteomics in Pulmonary Arterial Hypertension Risk Assessment?American journal of respiratory and critical care medicine · 2022Article
- Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension.Circulation research · 2022Review
- Editorial: Calcium and pulmonary hypertension.Frontiers in physiology · 2022Article
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Authors and funding
16 authors.
Funding
Abstract
rationaleIdiopathic pulmonary arterial hypertension (IPAH) is usually without an identified genetic cause, despite clinical and molecular similarity to bone morphogenetic protein receptor type 2 mutation-associated heritable pulmonary arterial hypertension (PAH). There is phenotypic heterogeneity in IPAH, with a minority of patients showing long-term improvement with calcium channel-blocker therapy.
objectivesWe sought to identify gene variants (GVs) underlying IPAH and determine whether GVs differ in vasodilator-responsive IPAH (VR-PAH) versus vasodilator-nonresponsive IPAH (VN-PAH).
methodsWe performed whole-exome sequencing (WES) on 36 patients with IPAH: 17 with VR-PAH and 19 with VN-PAH. Wnt pathway differences were explored in human lung fibroblasts. MEASUREMENTS AND MAIN
resultsWe identified 1,369 genes with 1,580 variants unique to IPAH. We used a gene ontology approach to analyze variants and identified overrepresentation of several pathways, including cytoskeletal function and ion binding. By mapping WES data to prior genome-wide association study data, Wnt pathway genes were highlighted. Using the connectivity map to define genetic differences between VR-PAH and VN-PAH, we found enrichment in vascular smooth muscle cell contraction pathways and greater genetic variation in VR-PAH versus VN-PAH. Using human lung fibroblasts, we found increased stimulated Wnt activity in IPAH versus controls.
conclusionsA pathway-based analysis of WES data in IPAH demonstrated multiple rare GVs that converge on key biological pathways, such as cytoskeletal function and Wnt signaling pathway. Vascular smooth muscle contraction-related genes were enriched in VR-PAH, suggesting a potentially different genetic predisposition for VR-PAH. This pathway-based approach may be applied to next-generation sequencing data in other diseases to uncover the contribution of unexpected or multiple GVs to a phenotype.
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