ArticleJournal of the American College of Cardiology2014
Disturbance in Z-disk mechanosensitive proteins induced by a persistent mutant myopalladin causes familial restrictive cardiomyopathy.
Article in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 51 citations in OpenAlex.
- Functional and Expression Studies of iPSC-Derived Cardiomyocytes Carrying a Novel HCM-AssociatedGenes · 2026Article
- Cardiomyopathy-associated and basic residue mutations in myopalladin alter actin binding, bundling, and structural stability.Protein science : a publication of the Protein Society · 2026Article
- Cardiac LIM Protein, Kidney Fibrosis, and Vascular Change after Acute Cardiorenal Syndrome.Journal of the American Society of Nephrology : JASN · 2025Article
- Research progress of ankyrin repeat domain 1 protein: an updated review.Cellular & molecular biology letters · 2024Review
- hsa-miR-548v controls the viscoelastic properties of human cardiomyocytes and improves their relaxation rates.JCI insight · 2024Article
- Associations of MYPN, TTN, SCN5A, MYO6 and ELN Mutations With Arrhythmias and Subsequent Sudden Cardiac Death: A Case Report of an Ecuadorian Individual.Cardiology research · 2023Article
- Genotype-Phenotype Associations with Restrictive Cardiomyopathy Induced by Pathogenic Genetic Mutations.Reviews in cardiovascular medicine · 2022Review
- Clinical genetic testing in four highly suspected pediatric restrictive cardiomyopathy cases.BMC cardiovascular disorders · 2022Article
- Progressive Reduction in Right Ventricular Contractile Function Attributable to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy.Circulation · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Systems genetics analysis defines importance of TMEM43/Physiological genomics · 2022Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- Article
- The Role of Z-disc Proteins in Myopathy and Cardiomyopathy.International journal of molecular sciences · 2021Review
- Cardiac Filaminopathies: Illuminating the Divergent Role of Filamin C Mutations in Human Cardiomyopathy.Journal of clinical medicine · 2021Review
- Genetic Restrictive Cardiomyopathy: Causes and Consequences-An Integrative Approach.International journal of molecular sciences · 2021Review
- A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1.Frontiers in physiology · 2021Article
- Modeling Cardiac Disease Mechanisms Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Progress, Promises and Challenges.International journal of molecular sciences · 2020Review
- Myopalladin promotes muscle growth through modulation of the serum response factor pathway.Journal of cachexia, sarcopenia and muscle · 2020Article
- Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies.International journal of molecular sciences · 2019Review
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14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFamilial restrictive cardiomyopathy (FRCM) has a poor prognosis due to diastolic dysfunction and restrictive physiology (RP). Myocardial stiffness, with or without fibrosis, underlie RP, but the mechanism(s) of restrictive remodeling is unclear. Myopalladin (MYPN) is a messenger molecule that links structural and gene regulatory molecules via translocation from the Z-disk and I-bands to the nucleus in cardiomyocytes. Expression of N-terminal MYPN peptide results in severe disruption of the sarcomere.
objectivesThe aim was to study a nonsense MYPN-Q529X mutation previously identified in the FRCM family in an animal model to explore the molecular and pathogenic mechanisms of FRCM.
methodsFunctional (echocardiography, cardiac magnetic resonance [CMR] imaging, electrocardiography), morphohistological, gene expression, and molecular studies were performed in knock-in heterozygote (Mypn(WT/Q526X)) and homozygote mice harboring the human MYPN-Q529X mutation.
resultsEchocardiographic and CMR imaging signs of diastolic dysfunction with preserved systolic function were identified in 12-week-old Mypn(WT/Q526X) mice. Histology revealed interstitial and perivascular fibrosis without overt hypertrophic remodeling. Truncated Mypn(Q526X) protein was found to translocate to the nucleus. Levels of total and nuclear cardiac ankyrin repeat protein (Carp/Ankrd1) and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Erk1/2), Erk1/2, Smad2, and Akt were reduced. Up-regulation was evident for muscle LIM protein (Mlp), desmin, and heart failure (natriuretic peptide A [Nppa], Nppb, and myosin heavy chain 6) and fibrosis (transforming growth factor beta 1, alpha-smooth muscle actin, osteopontin, and periostin) markers.
conclusionsHeterozygote Mypn(WT/Q526X) knock-in mice develop RCM due to persistence of mutant Mypn(Q526X) protein in the nucleus. Down-regulation of Carp and up-regulation of Mlp and desmin appear to augment fibrotic restrictive remodeling, and reduced Erk1/2 levels blunt a hypertrophic response in Mypn(WT/Q526X) hearts.
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