ArticleProceedings of the National Academy of Sciences of the United States of America2010
Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05167799 (Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction), which is not on this map. Cited by 162 papers, 2 of them syntheses that pooled it.
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.
Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction: a Multicentre Registry
Who cites it
162 citing papers in PubMed, 2 syntheses or guidelines pooled it, 322 citations in OpenAlex.
- Diagnostic Role of NT-proBNP in Patients with Cardiac Amyloidosis Involvement: A Meta-Analysis.Arquivos brasileiros de cardiologia · 2022Pooled it
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis.Blood advances · 2022Trial
- Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis.International journal of hematology · 2017Trial
- When Hematologic Response Does Not Translate to Cardiac Recovery in AL Amyloidosis.JACC. Case reports · 2026Article
- Proteomics Profiling Reveals Molecular Subtypes of Transthyretin Cardiac Amyloidosis.Circulation. Heart failure · 2026Article
- The Role of Cardiac Fibrosis and Fibroblast Activation in Amyloid Light Chain (AL) Amyloidosis.JACC. Basic to translational science · 2026Article
- Mechanistic Insights Into Metal Binding in the Aggregation Pathway of an Immunoglobulin Light Chain Protein.Chembiochem : a European journal of chemical biology · 2026Article
- Utilization and Prognosis of Cardiac Device Implantation in AL Versus ATTR Amyloidosis.Pacing and clinical electrophysiology : PACE · 2026Article
- Mechanisms of damage and therapies for cardiac amyloidosis: a role for inflammation?Clinical research in cardiology : official journal of the German Cardiac Society · 2026Review
- Infiltrative and Inflammatory Cardiomyopathies: Using Imaging to Probe Mechanisms of Myocardial Dysfunction.Journal of cardiac failure · 2026Review
- Exploring the MicroRNA Landscape in Cardiac Amyloidosis: Molecular Insights and Clinical Applications.Genes · 2026Review
- Evaluating natural history and treatment response in cardiac amyloidosis: the evolving role of multimodality imaging.European heart journal. Cardiovascular Imaging · 2026Review
- Multimodal Diagnosis of Cardiac Amyloidosis: Integrating Imaging, Histochemistry, and Proteomics of Precise Typing.International journal of molecular sciences · 2026Review
- Unveiling the unseen: navigating heart involvement in amyloidosis with biomarkers beyond the horizons of imaging.European heart journal. Imaging methods and practice · 2026Review
- Biomolecular mechanisms of cardiac amyloidosis and its cardiovascular pathological basis.Frontiers in immunology · 2026Review
- Amyloid Light Chain Proteins in Cardiovascular Disease: Pathogenesis and Emerging Therapies for Cardiac Amyloidosis.Pharmaceutical research · 2025Review
- Cardiac redox imbalance upon disruption of selenocysteine decomposition in mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- Mitochondrial Dysfunction in Cardiomyopathy and Heart Failure: From Energetic Collapse to Therapeutic Opportunity.Biomolecules · 2025Review
- Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.Journal of cardiovascular development and disease · 2025Review
102 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 8 institutions in 1 country.
Funding
Abstract
Patients with primary (AL) cardiac amyloidosis suffer from progressive cardiomyopathy with a median survival of less than 8 months and a 5-year survival of <10%. Contributing to this poor prognosis is the fact that these patients generally do not tolerate standard heart failure therapies. The molecular mechanisms underlying this deadly form of heart disease remain unclear. Although interstitial amyloid fibril deposition of Ig light chain proteins is a major cause of cardiac dysfunction in AL cardiac amyloidosis, we have previously shown that amyloid precursor proteins directly impair cardiac function at the cellular and isolated organ levels, independent of fibril formation. In this study, we report that amyloidogenic light chain (AL-LC) proteins provoke oxidative stress, cellular dysfunction, and apoptosis in isolated adult cardiomyocytes through activation of p38 mitogen-activated protein kinase (MAPK). AL-LC-induced p38 activation was found to be independent of the upstream MAPK kinase, MKK3/6, and instead depends upon transforming growth factor-beta-activated protein kinase-1 binding protein-1 (TAB1)-mediated p38alpha MAPK autophosphorylation. Treatment of cardiomyocytes with SB203580, a selective p38 MAPK inhibitor, significantly attenuated AL-LC-induced oxidative stress, cellular dysfunction, and apoptosis. Our data provide a unique mechanistic insight into the pathogenesis of AL-LC cardiac toxicity and suggest that TAB1-mediated p38alpha MAPK autophosphorylation may serve as an important event leading to cardiac dysfunction and subsequent heart failure.
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.