ArticleCirculation. Heart failure2022
Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility.
Article in Circulation. Heart failure, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Metabolomics in Pulmonary Hypertension-A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology.International journal of molecular sciences · 2023Pooled it
- Large animal models of right heart failure due to pulmonary hypertension: a bridge to translational success.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Multimodality Molecular Profiling Nominates Targetable Mechanisms in Progressive RV Dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Bazedoxifene Targets gp130 Signaling to Suppress Fibroblast Activation in Pathological Cutaneous Fibrosis: Insights from Spatial Transcriptomics and scRNA-seq Data.International journal of biological sciences · 2026Article
- Proteomic and metabolomic profiling nominates druggable targets and biomarkers for pulmonary arterial hypertension-associated myopathy and exercise intolerance in male monocrotaline rats.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025Article
- GP130 Antagonism Enhances Porcine RV Function.Circulation research · 2025Article
- A soft-stiff patterned bioengineering model reveals kinase pathways driving directional cell migration in pulmonary arterial hypertension.Biomaterials science · 2025Article
- Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025Review
- A Gut Feeling: Does the Gastrointestinal Tract Microbiome Contribute to the Pro-Inflammatory State in PAH?JACC. Basic to translational science · 2025Article
- The Impact of Insulin Resistance on Lung Volume Through Right Ventricular Dysfunction in Diabetic Patients-Literature Review.Journal of personalized medicine · 2025Review
- Article
- Right Ventricular Function, Inflammation, and the Gut Microbiome in Pulmonary Hypertension: A Translational Frontier.Circulation. Heart failure · 2025Article
- Dysfunctional cardiomyocyte signalling and heart disease.Current opinion in cell biology · 2025Review
- Glycoprotein 130 Antagonism Counteracts Metabolic and Inflammatory Alterations to Enhance Right Ventricle Function in Pulmonary Artery Banded Pigs.bioRxiv : the preprint server for biology · 2025Article
- Preparation of 18β-Glycyrrhetinic Acid Liposome and Its Therapeutic Effect on Pulmonary Arterial Hypertension.Drug design, development and therapy · 2025Article
- Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension.Circulation research · 2024Article
- Pathophysiology of the right ventricle and its pulmonary vascular interaction.The European respiratory journal · 2024Review
- Ferroptosis Integrates Mitochondrial Derangements and Pathological Inflammation to Promote Pulmonary Hypertension.bioRxiv : the preprint server for biology · 2024Article
- Multi-omic and multispecies analysis of right ventricular dysfunction.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Article
- AFrontiers in cardiovascular medicine · 2024Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRight ventricular dysfunction (RVD) is the leading cause of death in pulmonary arterial hypertension (PAH), but no RV-specific therapy exists. We showed microtubule-mediated junctophilin-2 dysregulation (MT-JPH2 pathway) causes t-tubule disruption and RVD in rodent PAH, but the druggable regulators of this critical pathway are unknown. GP130 (glycoprotein 130) activation induces cardiomyocyte microtubule remodeling in vitro; however, the effects of GP130 signaling on the MT-JPH2 pathway and RVD resulting from PAH are undefined.
methodsImmunoblots quantified protein abundance, quantitative proteomics defined RV microtubule-interacting proteins (MT-interactome), metabolomics evaluated the RV metabolic signature, and transmission electron microscopy assessed RV cardiomyocyte mitochondrial morphology in control, monocrotaline, and monocrotaline-SC-144 (GP130 antagonist) rats. Echocardiography and pressure-volume loops defined the effects of SC-144 on RV-pulmonary artery coupling in monocrotaline rats (8-16 rats per group). In 73 patients with PAH, the relationship between interleukin-6, a GP130 ligand, and RVD was evaluated.
resultsSC-144 decreased GP130 activation, which normalized MT-JPH2 protein expression and t-tubule structure in the monocrotaline RV. Proteomics analysis revealed SC-144 restored RV MT-interactome regulation. Ingenuity pathway analysis of dysregulated MT-interacting proteins identified a link between microtubules and mitochondrial function. Specifically, SC-144 prevented dysregulation of electron transport chain, Krebs cycle, and the fatty acid oxidation pathway proteins. Metabolomics profiling suggested SC-144 reduced glycolytic dependence, glutaminolysis induction, and enhanced fatty acid metabolism. Transmission electron microscopy and immunoblots indicated increased mitochondrial fission in the monocrotaline RV, which SC-144 mitigated. GP130 antagonism reduced RV hypertrophy and fibrosis and augmented RV-pulmonary artery coupling without altering PAH severity. In patients with PAH, higher interleukin-6 levels were associated with more severe RVD (RV fractional area change 23±12% versus 30±10%,
conclusionsGP130 antagonism reduces MT-JPH2 dysregulation, corrects metabolic derangements in the RV, and improves RVD in monocrotaline rats.
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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.