ArticleCirculation research2011
Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure.Nature communications · 2023Pooled it
- Effects of Continuous Accelerated Pacing on Cardiac Structure and Function in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the myPACE Randomized Clinical Trial.Journal of the American Heart Association · 2024Trial
- AKAP6β-a conductor in the orchestra of pathological cardiomyocyte gene transcription.Molecular pharmacology · 2026Review
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- mTORC1 and nuclear ERK spatially control translation in cardiomyocytes through 4EBP1 phosphorylation.Science signaling · 2026Article
- Eccentric Exercise and Muscle Damage: An Introductory Guide.Journal of functional morphology and kinesiology · 2026Review
- Gastrin ameliorates heart failure and suppresses myocardial remodeling via the JAK2/STAT3 and ERK1/2 pathways.PloS one · 2026Article
- The βCirculation research · 2025Article
- Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.Science (New York, N.Y.) · 2025Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Systems analysis reveals neuregulin-1 control of cardiomyocyte size and shape mediated by distinct PI3K and p38 pathways.bioRxiv : the preprint server for biology · 2025Article
- Persistence of cardiac malprogramming in late gestational fetal sheep by early to midgestational testosterone excess.American journal of physiology. Heart and circulatory physiology · 2025Article
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 2025Article
- Dual inhibition of TGFβ and PDGF improves RV remodeling and function in response to RV pressure or volume-loading.Physiological reports · 2025Article
- Article
- Cysteine-Rich Protein 61 (CCN1) Deficiency Alleviated Cardiac Remodeling in 5/6 Nephrectomized Mice by Suppressing the MAPK Signaling Pathway.Cardiovascular therapeutics · 2025Article
- YTHDF1 is pivotal for maintenance of cardiac homeostasis.Journal of molecular and cellular cardiology · 2024Article
- Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling.Circulation research · 2024Article
- Liquid-liquid phase separation in diseases.MedComm · 2024Review
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleAn increase in cardiac afterload typically produces concentric hypertrophy characterized by an increase in cardiomyocyte width, whereas volume overload or exercise results in eccentric growth characterized by cellular elongation and addition of sarcomeres in series. The signaling pathways that control eccentric versus concentric heart growth are not well understood.
objectiveTo determine the role of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in regulating the cardiac hypertrophic response. METHODS AND
resultsHere, we used mice lacking all ERK1/2 protein in the heart (Erk1(-/-) Erk2(fl/fl-Cre)) and mice expressing activated mitogen-activated protein kinase kinase (Mek)1 in the heart to induce ERK1/2 signaling, as well as mechanistic experiments in cultured myocytes to assess cellular growth characteristics associated with this signaling pathway. Although genetic deletion of all ERK1/2 from the mouse heart did not block the cardiac hypertrophic response per se, meaning that the heart still increased in weight with both aging and pathological stress stimulation, it did dramatically alter how the heart grew. For example, adult myocytes from hearts of Erk1(-/-) Erk2(fl/fl-Cre) mice showed preferential eccentric growth (lengthening), whereas myocytes from Mek1 transgenic hearts showed concentric growth (width increase). Isolated adult myocytes acutely inhibited for ERK1/2 signaling by adenoviral gene transfer showed spontaneous lengthening, whereas infection with an activated Mek1 adenovirus promoted constitutive ERK1/2 signaling and increased myocyte thickness. A similar effect was observed in engineered heart tissue under cyclic stretching, where ERK1/2 inhibition led to preferential lengthening.
conclusionsTaken together, these data demonstrate that the ERK1/2 signaling pathway uniquely regulates the balance between eccentric and concentric growth of the heart.
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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.