ArticleJournal of the American Heart Association2014
Reducing endoglin activity limits calcineurin and TRPC-6 expression and improves survival in a mouse model of right ventricular pressure overload.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Coordinated expression of BMP10/ALK1/endoglin-proteins that drive embryonic cardiac and vascular morphogenesis-in patients with heart failure: The EMPEROR Program.European journal of heart failure · 2025Article
- The unique hypertrophic and fibrotic features of neonatal right ventricle in response to pressure overload.Scientific reports · 2025Article
- CaBiomedicines · 2025Review
- Progress on role of ion channels of cardiac fibroblasts in fibrosis.Frontiers in physiology · 2023Review
- Proteomic Analysis Reveals Differential Expression Profiles in Idiopathic Pulmonary Fibrosis Cell Lines.International journal of molecular sciences · 2022Article
- Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology.Frontiers in physiology · 2022Review
- Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts.Cells · 2021Review
- TRPC Channels in Cardiac Plasticity.Cells · 2020Review
- Angiotensin-II-Evoked CaCells · 2020Article
- TRPC Channels: Dysregulation and CaCells · 2020Review
- CaJournal of cardiovascular development and disease · 2019Review
- CrossTalk proposal: The mouse SuHx model is a good model of pulmonary arterial hypertension.The Journal of physiology · 2019Article
- TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling.Frontiers in physiology · 2019Review
- Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.Circulation · 2018Article
- TGF-β Signaling in Control of Cardiovascular Function.Cold Spring Harbor perspectives in biology · 2018Review
- Roles and mechanisms of TRPC3 and the PLCγ/PKC/CPI-17 signaling pathway in regulating parturition.Molecular medicine reports · 2018Article
- Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Fibroblasts and the extracellular matrix in right ventricular disease.Cardiovascular research · 2017Review
- The Role of Endoglin in Myocardial Fibrosis.Acta Cardiologica Sinica · 2017Review
- Conditional knockout of activin like kinase-1 (ALK-1) leads to heart failure without maladaptive remodeling.Heart and vessels · 2017Article
Corrections and comments
- Erratum issuedUghreja, Kesahn [Corrected to Ughreja, Kishan]
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRight ventricular (RV) failure is a major cause of mortality worldwide and is often a consequence of RV pressure overload (RVPO). Endoglin is a coreceptor for the profibrogenic cytokine, transforming growth factor beta 1 (TGF-β1). TGF-β1 signaling by the canonical transient receptor protein channel 6 (TRPC-6) was recently reported to stimulate calcineurin-mediated myofibroblast transformation, a critical component of cardiac fibrosis. We hypothesized that reduced activity of the TGF-β1 coreceptor, endoglin, limits RV calcineurin expression and improves survival in RVPO. METHODS AND
resultsWe first demonstrate that endoglin is required for TGF-β1-mediated calcineurin/TRPC-6 expression and up-regulation of alpha-smooth muscle antigen (α-SMA), a marker of myofibroblast transformation, in human RV fibroblasts. Using endoglin haploinsufficient mice (Eng(+/-)) we show that reduced endoglin activity preserves RV function, limits RV fibrosis, and attenuates activation of the calcineurin/TRPC-6/α-SMA pathway in a model of angio-obliterative pulmonary hypertension. Next, using Eng(+/-) mice or a neutralizing antibody (Ab) against endoglin (N-Eng) in wild-type mice, we show that reduced endoglin activity improves survival and attenuates RV fibrosis in models of RVPO induced by pulmonary artery constriction. To explore the utility of targeting endoglin, we observed a reversal of RV fibrosis and calcineurin levels in wild-type mice treated with a N-Eng Ab, compared to an immunoglobulin G control.
conclusionThese data establish endoglin as a regulator of TGF-β1 signaling by calcineurin and TRPC-6 in the RV and identify it as a potential therapeutic target to limit RV fibrosis and improve survival in RVPO, a common cause of death in cardiac and pulmonary disease.
Indexed as
Identifiers
What OpenQuestion holds
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.