BACKGROUND Excess fat deposition could induce phenotypic changes of perivascular adipose tissue (PVAT remodeling), which may promote the progression of atherosclerosis via modulation of adipocytokine secretion. However, it remains unclear whether and how suppression of PVAT remodeling could attenuate vascular injury. In this study, we examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, luseogliflozin on PVAT remodeling and neointima formation after wire injury in mice. METHODS Wilt-type mice fed with low-fat diet (LFD) or high-fat diet (HFD) received oral administration of luseogliflozin (18 mg/kg/day) or vehicle. Mice underwent bilateral femoral artery wire injury followed by unilateral removal of surrounding PVAT. After 25 days, injured femoral arteries and surrounding PVAT were analyzed. RESULTS In LFD-fed lean mice, neither luseogliflozin treatment or PVAT removal attenuated the intima-to-media (I/M) ratio of injured arteries. However, in HFD-fed mice, luseogliflozin or PVAT removal reduced the I/M ratio, whereas their combination showed no additive reduction. In PVAT surrounding injured femoral arteries of HFD-fed mice, luseogliflozin treatment decreased the adipocyte sizes. Furthermore, luseogliflozin reduced accumulation of macrophages expressing platelet-derived growth factor-B (PDGF-B) and increased adiponectin gene expression. Gene expression levels of Pdgf-b in PVAT were correlated with the I/M ratio. CONCLUSIONS Our present study suggests that luseogliflozin could attenuate neointimal hyperplasia after wire injury in HFD-fed mice partly via suppression of macrophage PDGF-B expression in PVAT. Inhibition of PVAT remodeling by luseogliflozin may be a novel therapeutic target for vascular remodeling after angioplasty.

中文翻译：

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Luseogliflozin可通过抑制血管周围脂肪组织重塑来减轻高脂饮食喂养小鼠的金属丝损伤后的内膜增生。

背景技术过多的脂肪沉积可能会诱发血管周围脂肪组织的表型变化（PVAT重塑），这可能通过调节脂肪细胞因子的分泌来促进动脉粥样硬化的发展。然而，目前尚不清楚是否以及如何抑制PVAT重塑可以减轻血管损伤。在这项研究中，我们检查了钠葡萄糖共转运蛋白2（SGLT2）抑制剂luseogliflozin对小鼠导线损伤后PVAT重塑和新内膜形成的影响。方法饲喂低脂饮食（LFD）或高脂饮食（HFD）的枯萎型小鼠口服口服luseogliflozin（18 mg / kg /天）或赋形剂。小鼠遭受双侧股动脉钢丝损伤，然后单侧切除周围的PVAT。25天后，分析了受损的股动脉和周围的PVAT。结果在LFD喂养的瘦小鼠中，Luseogliflozin治疗或PVAT去除均不能减弱受伤动脉的内膜对中膜（I / M）的比率。但是，在由HFD喂养的小鼠中，去葡糖胺或PVAT的去除降低了I / M比，而它们的组合未显示加性降低。在HFD喂养的小鼠受损股动脉周围的PVAT中，葡格列净治疗降低了脂肪细胞的大小。此外，吕格列净减少了表达血小板源性生长因子-B（PDGF-B）的巨噬细胞的积累，并增加了脂联素基因的表达。PVAT中Pdgf-b的基因表达水平与I / M比相关。结论我们的研究表明，路西格列净可以通过抑制PVAT中巨噬细胞PDGF-B的表达来减轻HFD喂养的小鼠导线损伤后的内膜增生。