ArticleJCI insight2021
Cardiac retinoic acid levels decline in heart failure.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 32 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Self-assembled chamber-like cardiac organoids for modeling cardiac chamber formation and cardiotoxicity assessment.Nature communications · 2026Article
- Plasma proteomics improves risk prediction in heart failure and reveals unique biology in chronic chagas cardiomyopathy.PLoS neglected tropical diseases · 2026Article
- Therapeutic Strategies Targeting the Kidney-Liver-Immune-Heart Network: Circadian and Mechanosensory Pathways in CKD-Associated Cardiac Injury.International journal of molecular sciences · 2026Review
- CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity.JACC. CardioOncology · 2026Article
- Retinoic acid promotes expression of inflammatory factors in proliferative adult human heart cells.American journal of physiology. Cell physiology · 2026Article
- Article
- Determination of Retinol, Cholecalciferol, α-Tocopherol and Phylloquinone Levels in Dogs with Dilated Cardiomyopathy: A Preliminary Study.Animals : an open access journal from MDPI · 2025Article
- Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in Postischemic Hearts.Circulation. Heart failure · 2025Article
- Region- and Cell-type-Resolved Multiomic Atlas of the Heart.Molecular & cellular proteomics : MCP · 2025Article
- Retinoic acid signaling and metabolism in heart failure.American journal of physiology. Heart and circulatory physiology · 2025Review
- Vitamin A deficiency and male-specific effects on heart function in mice.Biochemical and biophysical research communications · 2025Article
- Ferroptosis: A New Mechanism in Diabetic Cardiomyopathy.International journal of medical sciences · 2024Review
- Raising NADCirculation · 2023Article
- Fetal metabolic adaptations to cardiovascular stress in twin-twin transfusion syndrome.iScience · 2023Article
- Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice.Nature communications · 2023Article
- Relationship between disorders of the intestinal microbiota and heart failure in infants with congenital heart disease.Frontiers in cellular and infection microbiology · 2023Article
- Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild-type and β-carotene 9',10' oxygenase knockout mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Inhibition of RhoA and Cdc42 by miR-133a Modulates Retinoic Acid Signalling during Early Development of Posterior Cardiac Tube Segment.International journal of molecular sciences · 2022Article
- Role of cellular retinol-binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi-omic approach.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Although low circulating levels of the vitamin A metabolite, all-trans retinoic acid (ATRA), are associated with increased risk of cardiovascular events and all-cause mortality, few studies have addressed whether cardiac retinoid levels are altered in the failing heart. Here, we showed that proteomic analyses of human and guinea pig heart failure (HF) were consistent with a decline in resident cardiac ATRA. Quantitation of the retinoids in ventricular myocardium by mass spectrometry revealed 32% and 39% ATRA decreases in guinea pig HF and in patients with idiopathic dilated cardiomyopathy (IDCM), respectively, despite ample reserves of cardiac vitamin A. ATRA (2 mg/kg/d) was sufficient to mitigate cardiac remodeling and prevent functional decline in guinea pig HF. Although cardiac ATRA declined in guinea pig HF and human IDCM, levels of certain retinoid metabolic enzymes diverged. Specifically, high expression of the ATRA-catabolizing enzyme, CYP26A1, in human IDCM could dampen prospects for an ATRA-based therapy. Pertinently, a pan-CYP26 inhibitor, talarozole, blunted the impact of phenylephrine on ATRA decline and hypertrophy in neonatal rat ventricular myocytes. Taken together, we submit that low cardiac ATRA attenuates the expression of critical ATRA-dependent gene programs in HF and that strategies to normalize ATRA metabolism, like CYP26 inhibition, may have therapeutic potential.
Indexed as
Identifiers
What Socratic 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 Socratic graph.