ArticleAmerican journal of physiology. Cell physiology2015
cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Article
- Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats.International journal of molecular sciences · 2025Article
- Epigenetics of cardiomyopathies: the next frontier.Heart failure reviews · 2025Review
- Research progress on DNA hydroxymethylation in atrial fibrillation: a review.Frontiers in pharmacology · 2025Review
- Article
- Reduced DNMT1 levels induce cell apoptosis via upregulation of METTL3 in cardiac hypertrophy.Heliyon · 2024Article
- Prediction of diagnostic gene biomarkers for hypertrophic cardiomyopathy by integrated machine learning.The Journal of international medical research · 2023Article
- Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.Signal transduction and targeted therapy · 2022Review
- Maternal caffeine intake and DNA methylation in newborn cord blood.The American journal of clinical nutrition · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- The role and molecular mechanism of epigenetics in cardiac hypertrophy.Heart failure reviews · 2021Review
- Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning.Frontiers in cardiovascular medicine · 2020Article
- Experimental models of cardiac physiology and pathology.Heart failure reviews · 2019Review
- Epigenetics of metabolic syndrome.Physiological genomics · 2018Review
- Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification.Heart failure reviews · 2018Review
- Successful knock-in of Hypertrophic Cardiomyopathy-mutation R723G into the MYH7 gene mimics HCM pathology in pigs.Scientific reports · 2018Article
- cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool.eLife · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
cAMP is a highly regulated secondary messenger involved in many biological processes. Chronic activation of the cAMP pathway by catecholamines results in cardiac hypertrophy and fibrosis; however, the mechanism by which elevated cAMP leads to cardiomyopathy is not fully understood. To address this issue, we increased intracellular cAMP levels in HL-1 cardiomyocytes, a cell line derived from adult mouse atrium, using either the stable cAMP analog N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or phosphodiesterase (PDE) inhibitors caffeine and theophylline. Elevated cAMP levels increased cell size and altered expression levels of cardiac genes and micro-RNAs associated with hypertrophic cardiomyopathy (HCM), including Myh6, Myh7, Myh7b, Tnni3, Anp, Bnp, Gata4, Mef2c, Mef2d, Nfatc1, miR208a, and miR208b. In addition, DBcAMP altered the expression of DNA methyltransferases (Dnmts) and Tet methylcytosine dioxygenases (Tets), enzymes that regulate genomic DNA methylation levels. Changes in expression of DNA methylation genes induced by elevated cAMP led to increased global DNA methylation in HL-1 cells. In contrast, inhibition of DNMT activity with 5-azacytidine treatment decreased global DNA methylation levels and blocked the increased expression of several HCM genes (Myh7, Gata4, Mef2c, Nfatc1, Myh7b, Tnni3, and Bnp) observed with DBcAMP treatment. These results demonstrate that cAMP induces cardiomyocyte hypertrophy and altered HCM gene expression in vitro and that DNA methylation patterns mediate the upregulation of HCM genes induced by cAMP. These data identify a previously unknown mechanism by which elevated levels of cAMP lead to increased expression of genes associated with cardiomyocyte hypertrophy.
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