SGLT2 inhibition reduces atherosclerosis by enhancing lipoprotein clearance in Ldlr type 1 diabetic mice

Abstract

These data suggest that tighter glycemic control in diabetes can improve lipoprotein clearance exclusive of Ldlr, likely via HSPG and bile acid pathways, and has an overall net positive effect on atherosclerosis.

Hyperglycemia Aggravates Diet-Induced Coronary Artery Disease and Myocardial Infarction in SR-B1-Knockout/ApoE-Hypomorphic Mice

“…Similarly, STZ-treated mice fed the HFC diet exhibited a significant increase in the average necrotic core size (26.5 ± 1.9 vs 14.9 ± 2.2% of plaque size for STZ- vs control-treated mice that had been fed the HFC diet; Figures 3G – I ). This is consistent with observations that STZ-treatment increases high fat diet-induced atherosclerosis in other mouse models such as low density receptor-deficient mice ( Vikramadithyan et al, 2005 ; Johnson et al, 2011 ; Al-Sharea et al, 2018 ).…”

“…In fact, children with type 1 diabetes exhibit increased aortic intima-media thickness, an early marker of subclinical atherosclerosis ( Harrington et al, 2010 ). Studies in animal models, such as atherosclerosis susceptible mice, have revealed that hyperglycemia is associated with increased aortic sinus atherosclerosis ( Park et al, 1998 ; Vikramadithyan et al, 2005 ; Werstuck et al, 2006 ; Johnson et al, 2011 ; Veerman et al, 2013 ; Venegas-Pino et al, 2013 ; Al-Sharea et al, 2018 ). However, the effects of hyperglycemia on coronary artery atherosclerosis are less well-studied, in part because conventional mouse atherosclerosis models, such as apolipoprotein E (apoE) or LDLR deficient mice, do not develop substantial coronary artery atherosclerosis or subsequent myocardial infarction ( Gonzalez et al, 2016 ; Trigatti and Fuller, 2016 ).…”

Empagliflozin Protects Atherosclerosis Progression by Modulating Lipid Profiles and Sympathetic Activity

“…Previous studies have also demonstrated that SGLT2 inhibitors reduce the development of atherosclerotic lesions in diabetic and non-diabetic mice [13][14][15][16]. Our results were consistent with these studies.…”

“…However, the effect of SGLT2 inhibitors on lipid pro les is not consistent in animal studies. Several previous studies have shown that SGLT2 inhibitors can lower lipid levels [14,19,20], while others have not [21][22][23][24][25]. Our results showed that empagli ozin could reduce the levels of triglyceride, total cholesterol and LDL, while there was no signi cant difference in HDL between the two groups.…”

“…And dapagli ozin could improve the differentiation of epicardial adipose tissue and perivascular adipose tissue [28]. In addition, SGLT2 inhibitor could enhance lipoprotein clearance through heparan sulfate proteoglycans (HSPG) and bile acid pathways [14], which could protect from atherosclerosis progression. In our article, we broaden our understanding of bene cial effect of SGLT2 inhibitor empagli ozin on the progression of atherosclerosis.…”