Simtuzumab, a monoclonal antibody targeting LOXL2, significantly attenuates myocardial fibrosis and prevents the decline of left ventricular function in LMNA-associated dilated cardiomyopathy models.
LMNA mutations (p.His222Pro) lead to structural nuclear abnormalities and disrupted chromosome spatial organization, which triggers the upregulation of pro-fibrotic genes, specifically LOXL2.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with LMNA mutations exhibit diastolic calcium overload and reduced contractile force in 3D engineered heart tissues.
Targeting the extracellular matrix (ECM) remodeling pathway via LOXL2 inhibition offers a disease-modifying strategy for patients with aggressive laminopathies.
Background: The Clinical Challenge of LMNA Mutations
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This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
