Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Dapagliflozin Stabilizes Diabetes-Induced Atherosclerotic Plaque Instability
Loading...
Citations
Altmetric:
Altmetric::
Download
Associated Records
Authors
File Licence
Editors
Date
2022-01-01
Source Title
Journal of the American Heart Association
Journal Title
Journal ISSN
Volume Title
Publisher
WILEY
Melbourne Authors
Affiliation
Melbourne Medical School
Document Type
Journal Article
Subject Code
Citation
Chen, Y. C., Jandeleit-Dahm, K. & Peter, K. (2022). Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Dapagliflozin Stabilizes Diabetes-Induced Atherosclerotic Plaque Instability. Journal of the American Heart Association, 11 (1), https://doi.org/10.1161/JAHA.121.022761.
Access Status
Open Access
Access URL
Open Access URL
Open Access at PMC
Linked Resource URL
NHMRC Grant Code
ARC Grant Code
Description
Abstract
Background Diabetes is known to accelerate atherosclerosis and increase plaque instability. However, there has been a lack of suitable animal models to study the effect of diabetes on plaque instability. We hypothesized that the tandem stenosis mouse model, which reflects plaque instability/rupture as seen in patients, can be applied to study the effects of diabetes and respective therapeutics on plaque instability/rupture. Methods and Results ApoE-/- mice at 7 weeks of age were rendered diabetic with streptozotocin and 5 weeks later were surgically subjected to tandem stenosis in the right carotid artery and fed with a high-fat diet for 7 weeks. As a promising new antidiabetic drug class, a sodium glucose co-transporter 2 inhibitor was tested in this new model. Diabetic mice showed an increase in the size of unstable atherosclerotic plaques and in the plaque instability markers MCP-1, CD68, and necrotic core size. Mice treated with dapagliflozin demonstrated attenuated glucose and triglyceride levels. Importantly, these mice demonstrated plaque stabilization with enhanced collagen accumulation, increased fibrosis, increased cap-to-lesion height ratios, and significant upregulation of the vasculoprotective NADPH oxidase 4 expression. Conclusions The tandem stenosis mouse model in combination with the application of streptozotocin represents a highly suitable and unique mouse model for studying plaque destabilization under diabetic conditions. Furthermore, for the first time, we provide evidence of plaque-stabilizing effects of sodium-glucose co-transporter 2 inhibitor. Our data also suggest that this newly developed mouse model is an attractive preclinical tool for testing antidiabetic drugs for the highly sought-after potential to stabilize atherosclerotic plaques.