TY - JOUR ID - 20932 TI - Inhibition of FABP4 attenuates cardiac fibrosis through inhibition of NLRP3 inflammasome activation JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Zhu, Xi AU - Zhang, Xiaogang AU - Cong, Xinpeng AU - Zhu, Luoning 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 - 10 SP - 1260 EP - 1266 KW - Cardiac fibrosis KW - Collagen KW - FABP4 KW - Fibroblast KW - NLRP3 inflammasome DO - 10.22038/ijbms.2022.64499.14186 N2 - Objective(s): Cardiac fibrosis is a key biological process of cardiac remodeling and heart failure. Fatty acid-binding protein 4 (FABP4) is a lipid-binding protein that can regulate glucose and lipid homeostasis, and its expression was elevated in heart failure. However, whether FABP4 is involved in cardiac fibrosis remains unknown. Materials and Methods: The cardiac fibrosis model was established in male C57BL/6 mice with subcutaneously infused angiotensin II (Ang-II) (2.8 mg/kg/day) for 4 weeks. DMSO or FABP4 inhibitor BMS309403 (50 mg/kg/day) was intraperitoneally injected for 4 weeks. Ang II-infused mice, FABP4 inhibitor (BMS309403) injected mice, and ventricular tissue were used for morphological studies, and histological and biochemical analyses (FABP4 protein composition and expression).Results: Ang II infusion increased FABP4 mRNA and protein expression in the mouse ventricular tissue. After treatment with FABP4 inhibitor BMS309403 for 4 weeks, mice showed improved cardiac structure and function as detected by echocardiography. BMS309403 suppressed cardiac and systemic inflammatory response, reduced collagen deposition, and mRNA expression of collagen type I (COL1A1) and collagen type III (COL3A1) in Ang II-infused mice. BMS309403 also reduced the number of α-smooth muscle actin (α-SMA)+cells and decreased the mRNA expression of α-SMA, matrix metalloproteinases-2 (MMP-2), MMP-9, and transforming growth factor-β (TGF‑β) in ventricular tissue.Conclusion: The inhibitory effect of BMS309403 on cardiac fibrosis might be associated with inhibition of NLRP3 inflammasome activation, which Ang II activated. Thus, our data speculated that inhibition of FABP4 could significantly induce cardiac fibrosis. UR - https://ijbms.mums.ac.ir/article_20932.html L1 - https://ijbms.mums.ac.ir/article_20932_b29db0eb0826dd64bc30dd96cd5c5f7f.pdf ER -