ArticleJournal of cellular and molecular medicine2016
Epigenetic silencing of TIMP4 in heart failure.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- DNA Methylation: A Key Epigenetic Regulator of Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Exploratory study of serum protein biomarkers for sudden cardiac arrest using protein extension assay: A case-control study.PloS one · 2025Article
- Epigenetics in Heart Failure.International journal of molecular sciences · 2024Review
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Identification of Novel Protein Biomarkers and Drug Targets for Acne Vulgaris by Integrating Human Plasma Proteome with Genome-Wide Association Data.Journal of inflammation research · 2024Article
- Tissue inhibitor of metalloproteinase-4 deletion in mice impacts maternal cardiac function during pregnancy and postpartum.American journal of physiology. Heart and circulatory physiology · 2023Article
- Ezh2 Inhibits Replicative Senescence of Atrial Fibroblasts Through Promotion of H3K27me3 in the Promoter Regions of CDKN2a and Timp4 Genes.Journal of inflammation research · 2022Article
- MicroRNA-146b-5p promotes atrial fibrosis in atrial fibrillation by repressing TIMP4.Journal of cellular and molecular medicine · 2021Article
- The role and molecular mechanism of epigenetics in cardiac hypertrophy.Heart failure reviews · 2021Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue inhibitor of matrix metalloprotease 4 (TIMP4) is endogenously one of the key modulators of matrix metalloprotease 9 (MMP9) and we have reported earlier that cardiac specific TIMP4 instigates contractility and helps in differentiation of cardiac progenitor cells. Although studies show that the expression of TIMP4 goes down in heart failure but the mechanism is unknown. This study aims to determine the mechanism of silencing of TIMP4 in heart failure progression created by aorta-vena cava (AV) fistula. We hypothesize that there is epigenetic silencing of TIMP4 in heart failure. To validate this hypothesis, we created heart failure model by creating AV fistula in C57BL/6 mice and looked into the promoter methylation (methylation specific PCR, high resolution melting, methylation sensitive restriction enzyme and Na bisulphite treatment followed by sequencing), histone modification (ChIP assay) and microRNAs that regulate TIMP4 (mir122a) and MMP9 (mir29b and mir455-5p). The physiological parameters in terms of cardiac function after AV fistula were assessed by echocardiography. We observed that there are 7 CpG islands in the TIMP4 promoter which get methylated during the progression of heart failure which leads to its epigenetic silencing. In addition, the up-regulated levels of mir122a in part, contribute to regulation of TIMP4. Consequently, MMP9 gets up-regulated and leads to cardiac remodeling. This is a novel report to explain the epigenetic silencing of TIMP4 in heart failure.
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Registered trials
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