Key result
Ipragliflozin induced healthy adipose expansion in abdominal perivascular adipose tissue, which attenuated cuff-induced neointimal hyperplasia and vascular remodeling in mice.
Why the study?
It was unclear whether SGLT2 inhibition in type 2 diabetes affects perivascular adipose tissue characteristics and whether resulting changes in adipose-derived secretory factors influence vascular pathophysiology.
Does ipragliflozin improve perivascular adipose tissue characteristics and prevent vascular remodeling in Western-type diet-fed mice?
Does ipragliflozin improve perivascular adipose tissue characteristics and prevent vascular remodeling in Western-type diet-fed mice?
p-value: p=<0.05
Ipragliflozin induces healthy expansion of perivascular adipose tissue, which attenuates inflammation and prevents vascular remodeling in a mouse model.
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.
No takes yet. Share an insight, caveat, or question.
Mori et al. (2019) studied Western-type diet-induced obesity and vascular remodeling. Ipragliflozin vs. Vehicle was evaluated on Cuff-induced neointimal hyperplasia (intima/media ratio) (p=<0.05). Ipragliflozin induced healthy adipose expansion in abdominal perivascular adipose tissue, which attenuated cuff-induced neointimal hyperplasia and vascular remodeling in mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: