Ipragliflozin-induced adipose expansion inhibits cuff-induced vascular remodeling in mice

Cardiovascular Diabetology

Yoshihiro Ogawa¹  Yasutaka Miyachi²  Kumiko Shiba²  Kyoichiro Tsuchiya³  Kentaro Mori³  Suguru Nakamura³  Kenichiro Kitamura³ 

[1]Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University

[2]Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

[3]Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi

关键词: Vascular remodeling;    Perivascular adipose tissue;    Healthy adipose expansion;    Cuff injury;   

DOI  :  10.1186/s12933-019-0886-1

来源: DOAJ

【 摘 要 】

Abstract Background Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. It is unclear whether inhibition of sodium glucose cotransporter 2 (SGLT2) in subjects with type 2 diabetes (T2DM) could affect PVAT characters, and whether the SGLT2 inhibitors-induced changes of adipose tissue, especially the alternation of adipose tissue-derived secretory factors, affect vascular pathophysiology. Methods Western-type diet (WD) fed wild-type mice were treated with or without an SGLT2 inhibitor ipragliflozin (Ipra) for 10 weeks. WEHI 274.1 and primary vascular smooth muscle cells were incubated with conditioned media (CM) of epididymal adipose tissue (Epi) or abdominal PVAT of Ipra- or vehicle-treated mice fed a WD. Epi of Ipra- or vehicle-treated mice fed a WD was implanted onto cuff-placed femoral arteries of apoE-deficient mice. Results Ipra increased adipocyte size associated with decreased expression of pro-inflammatory and fibrosis-related genes in abdominal PVAT of WD-fed mice. Ipra also suppressed WD-induced macrophages accumulation, fibrosis, and adipocyte death in abdominal PVAT. In CM of abdominal PVAT from Ipra-treated mice, concentration of leptin was significantly lower than that from vehicle-treated mice. In vitro, migration of WEHI 274.1 and primary vascular smooth muscle cells were more enhanced by CM of Epi or abdominal PVAT from vehicle-treated mice than that from Ipra-treated mice. Perivascular implantation of Epi from Ipra-treated mice to apolipoprotein E-deficient mice attenuated cuff-induced neointimal hyperplasia and vascular remodeling compared to that from vehicle-treated mice. Conclusions The Ipra-induced changes of abdominal PVAT will lead to a better understanding of unveiled mechanisms by which SGLT2 inhibitors prevent cardiovascular complications in T2DM, and the development of new therapeutic strategies targeting PVAT.

【 授权许可】

Unknown