Luseogliflozin attenuates neointimal hyperplasia after wire injury in high-fat diet-fed mice via inhibition of perivascular adipose tissue remodeling

• DOI: 10.1186/s12933-019-0947-5
• Publication Date: 2019-10-31T15:04:39Z
• Authors: Yusaku Mori; Michishige Terasaki; Munenori Hiromura; Tomomi Saito; Hideki Kushima; Masakazu Koshibu; Naoya Osaka; Makoto Ohara; Tomoyasu Fukui; Hirokazu Ohtaki; Hirano Tsutomu; Sho-ichi Yamagishi
• Keywords: Neointima; Neointimal hyperplasia; Platelet-derived growth factor

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