ArticleScience translational medicine2019
Activin type II receptor signaling in cardiac aging and heart failure.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07202000 (Double-blind, Prospective, Randomized, Placebo-controlled Trial to Assess if Activin Ligand-trap Biological Therapy Can Improve Exercise Capacity and Cognitive Function in Heart Failure With Preserved Ejection Fraction Compared to Placebo.), which is not on this map. Cited by 105 papers.
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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.
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.
Double-blind, Prospective, Randomized, Placebo-controlled Trial to Assess if Activin Ligand-trap Biological Therapy Can Improve Exercise Capacity and Cognitive Function in Heart Failure With Preserved Ejection Fraction Compared to Placebo.
Who cites it
105 citing papers in PubMed, 142 citations in OpenAlex.
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- Ligand-based directed differentiation to produce granulosa-like cells expressing steroidogenic enzyme genes.Stem cell research · 2026Article
- Identification and verification of biomarkers associated with integrated stress response in heart failure.Scientific reports · 2026Article
- Cardiovascular complications of pregnancy.The Journal of clinical investigation · 2026Review
- Cleaning, Chasing and Calming: Promising Paradigms of Senotherapy in Aging-Related Diseases.International journal of biological sciences · 2026Review
- Cardiomyocyte-Specific RNF128 Attenuates Pathological Cardiac Hypertrophy Progression by Stabilizing SERCA2a through Lys63-Linked Polyubiquitination.Theranostics · 2026Article
- Cardiovascular remodeling: key mechanisms and clinical implications linking sarcopenia and heart failure.Frontiers in medicine · 2026Review
- Elevated circulating GDF11 and its role in age-related sarcopenia: insights from clinical, transcriptomic, andFrontiers in aging · 2026Article
- RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2026Article
- ZNF454-FSTL3 axis inhibits colorectal cancer progression by inhibiting HIF-1α-mediated glycolysis in hypoxia.Journal of gastrointestinal oncology · 2025Article
- p22Nature cardiovascular research · 2025Article
- Cardiac ageing: from hallmarks to therapeutic opportunities.Cardiovascular research · 2025Review
- Plasma Proteomics Reveals Dysregulated Pathways Across the SpectrumCirculation. Genomic and precision medicine · 2025Article
- Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure.Nature communications · 2025Article
- Ligand-specific regulation of a binary enhancer code dictating cellular senescence.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues.ESC heart failure · 2025Review
- GDF10 promotes rodent cardiomyocyte maturation during the postnatal period.Journal of molecular and cellular cardiology · 2025Article
- Identification of aberrantly expressed genes during aging in the mouse heart via integrated bioinformatics analysis.Medicine · 2025Article
- Identification of arachidonic acid metabolism-related diagnostic markers in heart failure based on bioinformatics analysis and machine learning.Frontiers in cardiovascular medicine · 2025Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 10 institutions in 2 countries.
Funding
Abstract
Activin type II receptor (ActRII) ligands have been implicated in muscle wasting in aging and disease. However, the role of these ligands and ActRII signaling in the heart remains unclear. Here, we investigated this catabolic pathway in human aging and heart failure (HF) using circulating follistatin-like 3 (FSTL3) as a potential indicator of systemic ActRII activity. FSTL3 is a downstream regulator of ActRII signaling, whose expression is up-regulated by the major ActRII ligands, activin A, circulating growth differentiation factor-8 (GDF8), and GDF11. In humans, we found that circulating FSTL3 increased with aging, frailty, and HF severity, correlating with an increase in circulating activins. In mice, increasing circulating activin A increased cardiac ActRII signaling and FSTL3 expression, as well as impaired cardiac function. Conversely, ActRII blockade with either clinical-stage inhibitors or genetic ablation reduced cardiac ActRII signaling while restoring or preserving cardiac function in multiple models of HF induced by aging, sarcomere mutation, or pressure overload. Using unbiased RNA sequencing, we show that activin A, GDF8, and GDF11 all induce a similar pathologic profile associated with up-regulation of the proteasome pathway in mammalian cardiomyocytes. The E3 ubiquitin ligase, Smurf1, was identified as a key downstream effector of activin-mediated ActRII signaling, which increased proteasome-dependent degradation of sarcoplasmic reticulum Ca
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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.