ArticleCirculation2018
Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.
Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Nuclear Proteome Map of Mouse Heart Chambers.Molecular & cellular proteomics : MCP · 2026Article
- AH001: A New Drug Targeting RhoA in Heart Failure.Circulation research · 2026Article
- Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy.Apoptosis : an international journal on programmed cell death · 2025Review
- Myocardin-related transcription factor regulates actomyosin contractility and apical junction remodeling during vertebrate neural tube closure.Development (Cambridge, England) · 2025Article
- Heart failure with preserved ejection fraction in pigs causes shifts in posttranscriptional checkpoints.American journal of physiology. Heart and circulatory physiology · 2024Article
- Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.iScience · 2024Article
- A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Network model integrated with multi-omic data predicts MBNL1 signals that drive myofibroblast activation.iScience · 2023Article
- Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.Nature communications · 2022Article
- Mechanosensation mediates volume adaptation of cardiac cells and spheroids in 3D.Materials today. Bio · 2022Article
- The Function of SUMOylation and Its Critical Roles in Cardiovascular Diseases and Potential Clinical Implications.International journal of molecular sciences · 2021Review
- Review
- MRTF-A regulates myoblast commitment to differentiation by targeting PAX7 during muscle regeneration.Journal of cellular and molecular medicine · 2021Article
- A myocardin-adjacent lncRNA balances SRF-dependent gene transcription in the heart.Genes & development · 2021Article
- Cardiac fibrosis.Cardiovascular research · 2021Review
- Current Advances in 3D Tissue and Organ Reconstruction.International journal of molecular sciences · 2021Review
- Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Myeloid MKL1 Disseminates Cues to Promote Cardiac Hypertrophy in Mice.Frontiers in cell and developmental biology · 2021Article
- MBNL1 regulates isoproterenol-induced myocardial remodelling in vitro and in vivo.Journal of cellular and molecular medicine · 2021Article
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Authors and funding
16 authors at 1 institution in 1 country.
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Abstract
backgroundHypertrophic cardiomyocyte growth and dysfunction accompany various forms of heart disease. The mechanisms responsible for transcriptional changes that affect cardiac physiology and the transition to heart failure are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling cardiomyocyte force transmission and propagation of electrical activity. The ID is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy.
methodsTransmission electron microscopy, confocal microscopy, and single-molecule localization microscopy were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor (MRTF)-A and MRTF-B specifically in adult cardiomyocytes to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling.
resultsWe found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure. Although mice lacking MRTFs in adult cardiomyocytes display normal cardiac physiology at baseline, pressure overload leads to rapid heart failure characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and cardiomyocyte adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by single-molecule localization microscopy may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target.
conclusionsOur study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates cross-talk between the actin and microtubule cytoskeleton and maintains ID integrity and cardiomyocyte homeostasis in heart disease.
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