ArticleCirculation2017
Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling.
Article in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 168 citations in OpenAlex.
- PVNJournal of neuroinflammation · 2026Article
- 20(S)-protopanaxatriol ameliorates cardiac hypertrophy by activating the AMPK/PGC-1α/PPARγ signaling pathway.Journal of ginseng research · 2026Article
- Changes in mRNA expression in the myocardium of rats with ventilator-induced myocardial injury.Scientific reports · 2026Article
- Cardiac fibroblast Foxm1 deficiency prevents pressure overload-induced cardiac remodeling via the Usp10/MKK6-p38γ MAPK axis.Cell death and differentiation · 2026Review
- Accumulation of newly synthesized docosahexaenoic acid plays an essential role in heart regeneration.Protein & cell · 2026Article
- Vascular Smooth Muscle Cell-Specific BCAT2 Deficiency Attenuates Diabetic Atherosclerotic Calcification via Histone Propionylation.Research (Washington, D.C.) · 2026Article
- ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming.International journal of biological sciences · 2026Article
- Methionine restriction alleviates kidney fibrosis through epigenetic repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis.Nature communications · 2025Article
- The dual role of ATF3 in myocardial repair through macrophage regulation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Targeting long-chain acylcarnitine accumulation to protect cardiac mitochondrial homeostasis after complete revascularization.Cell reports. Medicine · 2025Article
- Hepatic activating transcription factor 3 protects against systemic inflammation by attenuating lipotoxicity.Metabolism open · 2025Article
- Cardiac Myofibroblast-Derived Small Extracellular Vesicles Moderate Fibrotic Responses via piRNA-62788/PIWIL2-Mediated SRF Silencing.Journal of extracellular vesicles · 2025Article
- A Multiomics Approach to Defining Target-Organ Injury in Youths With Primary Hypertension: The SHIP AHOY Cohort.Journal of the American Heart Association · 2025Article
- Multiomic and electrophysiologic analyses reveal that an inherited MRC2 variant causes fibroblast dysfunction and increased atrial fibrillation susceptibility.American journal of physiology. Heart and circulatory physiology · 2025Article
- LARP1 acts as a key mediator in preventing angiotensin II-induced cardiac dysfunction and fibrosis.Cell & bioscience · 2025Article
- Dissecting regulatory non-coding GWAS loci reveals fibroblast causal genes with pathophysiological relevance to heart failure.Nature communications · 2025Article
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- FOXM1 Protects Against Myocardial Ischemia-Reperfusion Injury in Rodent and Porcine Models by Suppressing MKRN1-Dependent LKB1 Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Machine learning identification of key genes in cardioembolic stroke and atherosclerosis: their association with pan-cancer and immune cells.European journal of medical research · 2025Article
- The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy.International journal of molecular sciences · 2025Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHypertensive ventricular remodeling is a common cause of heart failure. However, the molecular mechanisms regulating ventricular remodeling remain poorly understood.
methodsWe used a discovery-driven/nonbiased approach to identify increased activating transcription factor 3 (ATF3) expression in hypertensive heart. We used loss/gain of function approaches to understand the role of ATF3 in heart failure. We also examined the mechanisms through transcriptome, chromatin immunoprecipitation sequencing analysis, and in vivo and in vitro experiments.
resultsATF3 expression increased in murine hypertensive heart and human hypertrophic heart. Cardiac fibroblast cells are the primary cell type expressing high ATF3 levels in response to hypertensive stimuli. ATF3 knockout (ATF3KO) markedly exaggerated hypertensive ventricular remodeling, a state rescued by lentivirus-mediated/miRNA-aided cardiac fibroblast-selective ATF3 overexpression. Conversely, conditional cardiac fibroblast cell-specific ATF3 transgenic overexpression significantly ameliorated ventricular remodeling and heart failure. We identified Map2K3 as a novel ATF3 target. ATF3 binds with the Map2K3 promoter, recruiting HDAC1, resulting in Map2K3 gene-associated histone deacetylation, thereby inhibiting Map2K3 expression. Genetic Map2K3 knockdown rescued the profibrotic/hypertrophic phenotype in ATF3KO cells. Last, we demonstrated that p38 is the downstream molecule of Map2K3 mediating the profibrotic/hypertrophic effects in ATF3KO animals. Inhibition of p38 signaling reduced transforming growth factor-β signaling-related profibrotic and hypertrophic gene expression, and blocked exaggerated cardiac remodeling in ATF3KO cells.
conclusionsOur study provides the first evidence that ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing Map2K3 expression and subsequent p38-transforming growth factor-β signaling. These results suggest that positive modulation of cardiac fibroblast ATF3 may represent a novel therapeutic approach against hypertensive cardiac remodeling.
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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.