METHODS: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.
RESULTS: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.
CONCLUSIONS: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.
方法:26名患有严重心力衰竭的受试者,射血分数降低,用SGLT-2i治疗与26例未经治疗的受试者相比,年龄匹配(54.0±2.1vs.55.3±2.1年,n.s.),体重指数(27.8±0.9vs.28.8±1.0kg/m2,n.s.)和左心室射血分数(20.7±0.5vs.23.2±1.7%,n.s.),计划进行心脏移植或机械支持植入的人,包括在研究中。对手术期间获得的EAT进行了复杂的代谢组学和基因表达分析。
结果:SGLT-2i改善了炎症,如脂肪组织中促炎基因的基因表达谱改善和免疫细胞向EAT的浸润减少所证明的。在代谢组学分析中注意到的用油酸富集醚脂质表明减少了铁中毒的倾向,可能进一步降低SGLT-2i治疗受试者EAT中的氧化应激。
结论:我们的结果显示SGLT-2i治疗的严重心力衰竭患者的EAT炎症降低,与没有这种疗法的心力衰竭患者相比。EAT炎症和代谢状态的调节可能代表了SGLT-2i相关心力衰竭患者心脏保护作用背后的新机制。