ArticlePloS one2016
Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Melatonin Ameliorates Isoproterenol-Induced Cardiac Fibrosis by Suppressing BIP/PERK/CHOP Signaling Pathways; Insights from In Silico and In vivo Studies.Cell biochemistry and biophysics · 2025Article
- Tauroursodeoxycholic acid-induced increase in ectopic muscle mineralization occurs exclusively in dystrophic muscles and is independent of endoplasmic reticulum stress.Scientific reports · 2025Article
- Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Comprehensive mendelian randomization reveals atrial fibrillation-breast cancer relationship and explores common druggable targets.Frontiers in pharmacology · 2024Article
- X-box Binding Protein 1: An Adaptor in the Pathogenesis of Atherosclerosis.Aging and disease · 2023Review
- Ryanodine receptor 2 (RYR2) dysfunction activates the unfolded protein response and perturbs cardiomyocyte maturation.Cardiovascular research · 2023Article
- Regulation of cardiac fibroblast cell death by unfolded protein response signaling.Frontiers in physiology · 2023Review
- Article
- IRE1/XBP1 and endoplasmic reticulum signaling - from basic to translational research for cardiovascular disease.Current opinion in physiology · 2022Article
- Calreticulin and the Heart.Cells · 2022Review
- Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.Nature reviews. Cardiology · 2021Review
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Changes in Intestinal Flora Structure and Metabolites Are Associated With Myocardial Fibrosis in Patients With Persistent Atrial Fibrillation.Frontiers in nutrition · 2021Article
- Inositol Requiring Enzyme (IRE), a multiplayer in sensing endoplasmic reticulum stress.Animal cells and systems · 2021Review
- Calsequestrin: a well-known but curious protein in skeletal muscle.Experimental & molecular medicine · 2020Review
- Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy.Matrix biology plus · 2020Article
- High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy.Circulation · 2020Article
- The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts.International journal of molecular sciences · 2020Article
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Selective enhancement of cardiomyocyte efficiency results in a pernicious heart condition.PloS one · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR) pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function. METHODOLOGY/PRINCIPAL
findingsWe demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER) homeostasis, transient activation of the unfolded protein response (UPR) pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA) is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.
conclusionsWe show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.
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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.