ArticleCirculation research2020
CITED4 Protects Against Adverse Remodeling in Response to Physiological and Pathological Stress.
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 59 citations in OpenAlex.
- Age-dependent effects of aerobic training on cardiac expression of Akt1, mTOR, and CITED4 in immature, young-adult, and middle-aged rat myocardium.European journal of applied physiology · 2026Article
- Pentose phosphate pathway-derived NADPH facilitates physiological hypertrophy and alleviates ischemia-reperfusion injury in the heart.Nature metabolism · 2026Article
- Exercise ModulatesInternational journal of molecular sciences · 2026Article
- Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats.Nature communications · 2026Article
- Concurrent Alterations in DNA Methylation and RNA m6A Methylation During Epigenetic and Transcriptomic Reprogramming Induced by Tail Docking Stress in Fat-Tailed Sheep.Animals : an open access journal from MDPI · 2026Article
- Transcriptomic insights into aerobic exercise-mediated attenuation of high-fat diet-induced muscle wasting.Frontiers in physiology · 2026Article
- CITED Proteins in Cardiac Development and Lifelong Heart Function.Journal of personalized medicine · 2025Review
- Modeling myocardial physiological growth using human pluripotent stem cell derived cardiomyocytes and 3D cardiac microtissues.Cellular and molecular life sciences : CMLS · 2025Article
- Cited4a limits cardiomyocyte dedifferentiation and proliferation during zebrafish heart regeneration.Development (Cambridge, England) · 2025Article
- Single-Cell Sequencing Identifies the Crucial Role of Mitochondrial Fission-Fusion Imbalance in Heart Failure Progression.Journal of cardiovascular translational research · 2025Article
- TargetingJournal of the American Heart Association · 2025Article
- Molecular Mediators of the Cardiac Benefits of Exercise.Circulation research · 2025Review
- Athlete's Heart Revisited: Historical, Clinical, and Molecular Perspectives.Circulation research · 2025Review
- Trbp inhibits cardiac fibrosis through TGF-β pathway-mediated cross-talk between cardiomyocytes and fibroblasts.Clinical science (London, England : 1979) · 2025Article
- Roles of Autophagy, Mitophagy, and Mitochondria in Left Ventricular Remodeling after Myocardial Infarction.Reviews in cardiovascular medicine · 2025Review
- Advances in MicroRNA Therapy for Heart Failure: Clinical Trials, Preclinical Studies, and Controversies.Cardiovascular drugs and therapy · 2025Review
- Exercise Mediates Noncoding RNAs in Cardiovascular Diseases: Pathophysiological Roles and Clinical Application.Expert reviews in molecular medicine · 2024Review
- HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.Molecular and cellular biochemistry · 2024Article
- CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Cited2 is a key regulator of placental development and plasticity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
rationaleCardiac CITED4 (CBP/p300-interacting transactivators with E [glutamic acid]/D [aspartic acid]-rich-carboxylterminal domain4) is induced by exercise and is sufficient to cause physiological hypertrophy and mitigate adverse ventricular remodeling after ischemic injury. However, the role of endogenous CITED4 in response to physiological or pathological stress is unknown.
objectiveTo investigate the role of CITED4 in murine models of exercise and pressure overload. METHODS AND
resultsWe generated cardiomyocyte-specific CITED4 knockout mice (C4KO) and subjected them to an intensive swim exercise protocol as well as transverse aortic constriction (TAC). Echocardiography, Western blotting, qPCR, immunohistochemistry, immunofluorescence, and transcriptional profiling for mRNA and miRNA (microRNA) expression were performed. Cellular crosstalk was investigated in vitro. CITED4 deletion in cardiomyocytes did not affect baseline cardiac size or function in young adult mice. C4KO mice developed modest cardiac dysfunction and dilation in response to exercise. After TAC, C4KOs developed severe heart failure with left ventricular dilation, impaired cardiomyocyte growth accompanied by reduced mTOR (mammalian target of rapamycin) activity and maladaptive cardiac remodeling with increased apoptosis, autophagy, and impaired mitochondrial signaling. Interstitial fibrosis was markedly increased in C4KO hearts after TAC. RNAseq revealed induction of a profibrotic miRNA network. miR30d was decreased in C4KO hearts after TAC and mediated crosstalk between cardiomyocytes and fibroblasts to modulate fibrosis. miR30d inhibition was sufficient to increase cardiac dysfunction and fibrosis after TAC.
conclusionsCITED4 protects against pathological cardiac remodeling by regulating mTOR activity and a network of miRNAs mediating cardiomyocyte to fibroblast crosstalk. Our findings highlight the importance of CITED4 in response to both physiological and pathological stimuli.
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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.