ArticleJournal of the American Heart Association2017
Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.
Article in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Association between salivary microbiota-related amino acid metabolic dysregulation and tacrolimus-induced gingival overgrowth following kidney transplantation.BMC oral health · 2026Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Precise coordination between nutrient transporters ensures fertility in the malaria mosquito Anopheles gambiae.PLoS genetics · 2024Article
- Article
- Characterization of a robust mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2023Article
- Ciclopirox Inhibition of eIF5A Hypusination Attenuates Fibroblast Activation and Cardiac Fibrosis.Journal of cardiovascular development and disease · 2023Article
- The emerging role of mass spectrometry-based proteomics in drug discovery.Nature reviews. Drug discovery · 2022Review
- Dietary therapy in abdominal aortic aneurysm - Insights from clinical and experimental studies.Frontiers in cardiovascular medicine · 2022Review
- The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease.Molecular therapy. Nucleic acids · 2021Review
- Halofuginone, a promising drug for treatment of pulmonary hypertension.British journal of pharmacology · 2021Article
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- The Multifaceted Roles of Proline in Cell Behavior.Frontiers in cell and developmental biology · 2021Review
- Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis.Circulation research · 2020Article
- Phexpo: a package for bidirectional enrichment analysis of phenotypes and chemicals.JAMIA open · 2020Article
- Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Research Progress on the Interaction Between Autophagy and Energy Homeostasis in Cardiac Remodeling.Frontiers in pharmacology · 2020Review
- Beyond Family: Modeling Non-hereditary Heart Diseases With Human Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in physiology · 2020Review
- Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production.Science signaling · 2019Article
- Halofuginone protects against advanced glycation end products‑induced injury of H9C2 cells via alleviating endoplasmic reticulum stress‑associated apoptosis and inducing autophagy.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
32 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure. METHODS AND
resultsConsistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-dependent activation of the AAR pathway in cardiac fibroblasts as evidenced by activation of known AAR target genes, broad regulation of the transcriptome and proteome, and reversal by l-proline supplementation. Halofuginone was examined in 3 mouse models of cardiac stress: angiotensin II/phenylephrine, transverse aortic constriction, and acute ischemia reperfusion injury. It activated the AAR pathway in the heart, improved survival, pulmonary congestion, left ventricle remodeling/fibrosis, and left ventricular function, and rescued ischemic myocardium. In human cardiac fibroblasts, halofuginone profoundly reduced collagen deposition in a general control nonderepressible 2-dependent manner and suppressed the extracellular matrix proteome. In human induced pluripotent stem cell-derived cardiomyocytes, halofuginone blocked gene expression associated with endothelin-1-mediated activation of pathologic hypertrophy and restored autophagy in a general control nonderepressible 2/eIF2α-dependent manner.
conclusionsHalofuginone activated the AAR pathway in the heart and attenuated the structural and functional effects of cardiac stress.
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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.