TY - JOUR ID - 20824 TI - LOXL2 silencing suppresses angiotensin II-induced cardiac hypertrophy through the EMT process and TGF-β1/Smad3/NF-κB pathway JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Luo, Jun AU - Wu, Yingbiao AU - Zhu, Xi AU - Wang, Saihua AU - Zhang, Xiaogang AU - Ning, Zhongping AD - Department of Cardiology, Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, Shanghai 201318, China Y1 - 2022 PY - 2022 VL - 25 IS - 8 SP - 964 EP - 969 KW - Angiotensin II KW - Atrial fibrillation KW - Epithelial-mesenchymal - transition KW - Hypertrophy KW - LOXL2 protein DO - 10.22038/ijbms.2022.63338.13981 N2 - Objective(s): Atrial fibrillation (AF) is a common arrhythmia with atrial myocyte hypertrophy linked with stroke, heart failure, and increased mortality. Lysyl oxidase-like 2 (LOXL2) involves the cross-linking of collagen in the extracellular matrix (ECM). In the present study, we investigated the roles and underlying mechanisms of LOXL2 on cardiomyocyte hypertrophy. Materials and Methods: The expression of LOXL2 mRNA and protein were detected in angiotensin II (Ang II) treated rat cardiomyocytes H9c2 by RT-qPCR and western blot. Small interfering RNA (siRNA) mediated LOXL2 gene silencing was used to evaluate cardiac hypertrophy and related markers. Also, the protein expression of EMT markers and Smad3/NF-κB pathway was determined by western blot. Results: Ang II significantly increased mRNA and protein expressions of LOXL2 and increased mRNA levels of myocardial hypertrophy markers, including ANP, BNP, and β-MHC in H9c2 cells. Silencing of LOXL2 significantly suppressed Ang II-induced hypertrophy and reversed the increase in ANP, BNP, and β-MHC mRNA levels. Also, EMT markers’ expressions, as evidenced by increased E-cadherin and decreased vimentin, α-smooth muscle actin (α-SMA), fibroblast-specific protein (FSP), and collagen 1A1. Mechanistically, we found that LOXL2 silencing suppressed protein expressions of TGF-β1, p-Smad3, and p-NF-κB in Ang II-stimulated H9c2 cells. LOXL2 silencing also attenuated Ang II-induced increased expression and content of proinflammatory cytokines IL-1β (H) and TNF-α. Conclusion: Our data speculated that LOXL2 might be a potential contributing factor to Ang II-induced cardiac hypertrophy, and TGF-β1/Smad3/NF-κB is involved in a signal axis and might be a potential strategy in treating cardiac hypertrophy.  UR - https://ijbms.mums.ac.ir/article_20824.html L1 - https://ijbms.mums.ac.ir/article_20824_407393c518ef38f9c211c447e09495be.pdf ER -