Key result
FABP4 inhibitor BMS309403 reduces LV mass ~17% and attenuates cardiac fibrosis in Ang II-infused mice.
Why the study?
FABP4 expression is elevated in heart failure, but whether it is involved in cardiac fibrosis remains unknown.
Does the FABP4 inhibitor BMS309403 attenuate cardiac fibrosis in an Ang II-infused mouse model?
Does the FABP4 inhibitor BMS309403 attenuate cardiac fibrosis in an Ang II-infused mouse model?
Inhibition of FABP4 with BMS309403 attenuates Ang II-induced cardiac fibrosis, likely through inhibition of NLRP3 inflammasome activation.
Answers are grounded in this paper and cite their sources.
Supports FABP4 inhibition in preclinical fibrosis models; leaves open human translation and trials.
Objectives: 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 (TGFβ) 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.
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Zhu et al. (2022) studied Cardiac fibrosis (n=24). BMS309403 (FABP4 inhibitor) vs. Angiotensin II (2.8 mg/kg/day) + DMSO was evaluated on Left ventricular mass (mg) (p=<0.001). Treatment with the FABP4 inhibitor BMS309403 significantly reduced left ventricular mass and attenuated cardiac fibrosis in Ang II-infused mice.
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