ArticleJournal of the American Heart Association2022
Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice.
Article in Journal of the American Heart Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- Airway smooth muscle in asthma: insights from a transcriptomic meta-analysis.ERJ open research · 2026Article
- SORBS2 regulates diastolic function through cytoskeletal networks and calcium handling.Communications biology · 2026Article
- A large-scale single-nucleus resource reveals a cardiomyocyte-like fibroblast and stage-specific remodeling across cardiomyopathies.BMC medicine · 2026Article
- Shared splicing dysregulation in heart failure associated with dilated and ischaemic cardiomyopathy and spatial specificity across cardiac regions.Cardiovascular research · 2026Article
- SORBS2: A Molecular Nexus in Multisystem Diseases Through Scaffold-Mediated Regulation.Journal of cellular and molecular medicine · 2026Review
- Short SCN5A Transcript Yields a NaV1.5 Fragment Influencing Cardiac Metabolism.Circulation research · 2026Article
- Single-Cell Transcriptomics and Lineage Tracing Unveil Parallels in Lymphatic Muscle and Venous Smooth Muscle Development, Identity, and Function.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Impact of Sorbs2 dysfunction on cardiovascular diseases.Biochimica et biophysica acta. Molecular basis of disease · 2025Review
- Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition.Cardiovascular research · 2025Article
- Gain and loss of the centrosomal protein taxilin-beta influences cardiac proteostasis and stress.Journal of molecular and cellular cardiology · 2025Article
- Spatial visualization provides insight into immune modulation by an L-DBF vaccine formulation againstFrontiers in immunology · 2025Article
- Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.Journal of molecular and cellular cardiology plus · 2024Article
- Transcriptional, developmental, and functional parallels of lymphatic and venous smooth muscle.bioRxiv : the preprint server for biology · 2024Article
- Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes.Circulation research · 2024Article
- Comparative Proteomic and Phosphoproteomic Analyses Reveal Molecular Signatures of Myocardial Infarction and Transverse Aortic Constriction in Aged Mouse Models.Cardiology research and practice · 2024Article
- Increased cardiac macrophages inFrontiers in genetics · 2024Article
- Modulation of miR-29 influences myocardial compliance likely through coordinated regulation of calcium handling and extracellular matrix.Molecular therapy. Nucleic acids · 2023Article
- Suppression of RBFox2 by Multiple MiRNAs in Pressure Overload-Induced Heart Failure.International journal of molecular sciences · 2023Article
- TNF-α-induced Inhibition of Protein MyristoylationIn vivo (Athens, Greece)Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Background Sorbin and SH3 domain containing 2 (Sorbs2) protein is a cytoskeletal adaptor with an emerging role in cardiac biology and disease; yet, its potential relevance to adult-onset cardiomyopathies remains underexplored. Sorbs2 global knockout mice display lethal arrhythmogenic cardiomyopathy; however, the causative mechanisms remain unclear. Herein, we examine Sorbs2 dysregulation in heart failure, characterize novel Sorbs2 cardiomyocyte-specific knockout mice (Sorbs2-cKO), and explore associations between Sorbs2 genetic variations and human cardiovascular disease. Methods and Results Bioinformatic analyses show myocardial Sorbs2 mRNA is consistently upregulated in humans with adult-onset cardiomyopathies and in heart failure models. We generated Sorbs2-cKO mice and report that they develop progressive systolic dysfunction and enlarged cardiac chambers, and they die with congestive heart failure at about 1 year old. After 3 months, Sorbs2-cKO mice begin to show atrial enlargement and P-wave anomalies, without dysregulation of action potential-associated ion channel and gap junction protein expressions. After 6 months, Sorbs2-cKO mice exhibit impaired contractility in dobutamine-treated hearts and skinned myofibers, without dysregulation of contractile protein expressions. From our comprehensive survey of potential mechanisms, we found that within 4 months, Sorbs2-cKO hearts have defective microtubule polymerization and compensatory upregulation of structural cytoskeletal and adapter proteins, suggesting that this early intracellular structural remodeling is responsible for contractile dysfunction. Finally, we identified genetic variants that associate with decreased Sorbs2 expression and human cardiac phenotypes, including conduction abnormalities, atrial enlargement, and dilated cardiomyopathy, consistent with Sorbs2-cKO mice phenotypes. Conclusions Our studies show that Sorbs2 is essential for maintaining structural integrity in cardiomyocytes, likely through strengthening the interactions between microtubules and other cytoskeletal proteins at cross-link sites.
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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 Socratic graph.