Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of function LMNA mutation

Nucleus, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 9, 2025

Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations LMNA gene. Although hypothesis that NE from are a fundamental feature of striated muscle damage has garnered wide acceptance, molecular sequalae provoked by and how they underlie disease pathogenesis such as cardiomyopathy (LMNA cardiomyopathy) remain poorly understood. We recently shed light on one consequence, employing cardiomyocyte-specific Lmna deletion vivo adult heart. observed extensive prior to cardiac function deterioration collateral perinuclear space. The Golgi is particularly affected, leading cytoprotective stress responses likely disrupted progressive itself. In this review, we discuss etiology 'organelle trauma' nexus between pathogenesis.

Язык: Английский

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LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The genetic variants of LMNA cause an array diseases that often affect the heart. LMNA-related cardiomyopathy exhibits high-penetrance and early-onset phenotypes lead to late-stage heart failure or lethal arrhythmia. As a subtype dilated arrhythmogenic cardiomyopathy, cardiac dysfunction is resistant existing therapeutic strategies, leaving major unmet clinical need in management. Here we comprehensively summarize current knowledge about basis, disease models pathological mechanisms cardiomyopathy. Recent translational studies were highlighted indicate new modalities such as gene supplementation, silencing genome editing therapy, which offer potential opportunities overcome difficulties development specific drugs for this disease. involves many diverse preclude small-molecule target only small fraction mechanisms. Agreeing notion, first-in-human trial recently reported futility. By contrast, therapy offers hope directly intervene demonstrates tremendous breakthrough Concepts review are also applicable other lack effective therapeutics.

Язык: Английский

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Modeling Arrhythmia in a Dish: An Open View from Human-Engineered Heart Constructs

International Journal of Drug Discovery and Pharmacology, Год журнала: 2025, Номер unknown, С. 100001 - 100001

Опубликована: Янв. 6, 2025

Review Modeling Arrhythmia in a Dish: An Open View from Human-Engineered Heart Constructs Shiya Wang 1,†, Pengcheng Yang 1,2,†, Jonathan Nimal Selvaraj 1,* and Donghui Zhang 1,3,* 1 State Key Laboratory of Biocatalysts Enzyme Engineering, Stem Cells Tissue Engineering Manufacture Center, School Life Sciences, Hubei University, Wuhan 430062, China 2 Biomanufacturing Department Mechanical Tsinghua Beijing100084, 3 Cardiovascular Research Institute, Union Hospital, Tongji Medical College, Huazhong University Science Technology, 430022, * Correspondence: corresponding author:[email protected] (J.N.S.); [email protected] (D.Z.) † These authors contributed equally to this work. Received: 26 July 2024; Revised: 29 September Accepted: 30 Published: 6 February 2025 Abstract: Human-engineered heart constructs (hEHC), comprising cardiac organoids engineered tissues, have become essential for replicating pathological physiological mechanisms associated with development diseases. The ongoing advancements fabrication culture techniques these rendered them increasingly vital cardiotoxicity prediction drug efficacy evaluations. There is an escalating demand standardized methodologies encompassing uniform fabrication, accurate disease modeling, multidimensional phenotype assessments facilitate comprehensive understanding constructs. This review systematically examines hEHC, highlighting recent their cellular composition functional characteristics, while stressing the necessity thorough evaluations significant phenotype, particularly arrhythmia. Here, we propose novel modular classification model based on specific modeling parameters categorize existing research vitro assessment into various quantitative metrics. framework provides researchers innovative insights strategies personalized design evaluation.

Язык: Английский

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Evolving from organoid to assembloid with enhanced cellular interactions

Cell organoid (Print), Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models

Stem Cell Reports, Год журнала: 2025, Номер unknown, С. 102467 - 102467

Опубликована: Март 1, 2025

Язык: Английский

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Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Язык: Английский

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Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics

Medizinische Genetik, Год журнала: 2025, Номер 37(2), С. 137 - 146

Опубликована: Апрель 4, 2025

Язык: Английский

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Engineering immune organoids to regenerate host immune system

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 89, С. 102276 - 102276

Опубликована: Ноя. 6, 2024

Язык: Английский

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