Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function in LMNA Mutation-Induced Dilated Cardiomyopathy - PubMed
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- #Simtuzumab
- #cardiomyopathy
- #Loxl2
- Simtuzumab attenuates Loxl2-mediated extracellular matrix remodeling in LMNA mutation-induced dilated cardiomyopathy.
- LMNA mutations lead to arrhythmias, contractile dysfunction, and myocardial fibrosis, impairing left ventricular function.
- Human induced pluripotent stem cells (hiPSCs) and a murine model with LMNA mutation (c.665A>C, p.His222Pro) were used to study the disease.
- LMNA patient-derived cardiomyocytes showed elevated diastolic calcium levels, hypocontractility, and nuclear shape abnormalities.
- Transcriptomic analysis revealed dysregulation of extracellular matrix remodeling and significant upregulation of Loxl2 in mutated cells.
- Simtuzumab, a Loxl2 inhibitor, effectively prevented cardiac dysfunction and fibrosis in vivo.
- Loxl2 inhibition is a promising therapeutic strategy for LMNA-associated dilated cardiomyopathy.