The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice
Background. Our study aimed to observe the effect of sodium glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on diabetic atherosclerosis and investigate the subsequent mechanism. Methods. Aortic atherosclerosis was induced in streptozotocin induced diabetic ApoE−/− mice by feeding with high-f...
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/6305735 |
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| author | Weiling Leng Xinshou Ouyang Xiaotian Lei Mingxia Wu Liu Chen Qinan Wu Wuquan Deng Ziwen Liang |
| author_facet | Weiling Leng Xinshou Ouyang Xiaotian Lei Mingxia Wu Liu Chen Qinan Wu Wuquan Deng Ziwen Liang |
| author_sort | Weiling Leng |
| collection | DOAJ |
| description | Background. Our study aimed to observe the effect of sodium glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on diabetic atherosclerosis and investigate the subsequent mechanism. Methods. Aortic atherosclerosis was induced in streptozotocin induced diabetic ApoE−/− mice by feeding with high-fat diet, and dapagliflozin was administrated intragastrically for 12 weeks as treatment. Effects of dapagliflozin on indices of glucose and fat metabolism, IL-1β, IL-18, NLRP3 protein levels, and the reactive oxygen species (ROS) were measured. The atherosclerosis was evaluated by oil red O and hematoxylin-eosin staining. The effects of dapagliflozin on the IL-1β production in culturing primary macrophages of wild type and NLRP3−/− knockout mice were investigated for mechanism analyses. Results. Dapagliflozin treatment showed favorable effects on glucose and fat metabolism, partially reversed the formation of atherosclerosis, inhibited macrophage infiltration, and enhanced the stability of lesion. Also, reduced production of IL-1β, IL-18, NLRP3 protein, and mitochondrial ROS in the aortic tissues was detected with dapagliflozin treatment. In vitro, NLRP3 inflammasome was activated by hyperglucose and hyperlipid through ROS pathway. Conclusions. Dapagliflozin may be of therapeutic potential for diabetic atherosclerosis induced by high-fat diet, and these benefits may depend on the inhibitory effect on the secretion of IL-1β by macrophages via the ROS-NLRP3-caspase-1 pathway. |
| format | Article |
| id | doaj-art-866a9f5d4de74f0785abcaee4e1accb4 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-866a9f5d4de74f0785abcaee4e1accb42025-02-03T01:24:21ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/63057356305735The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− MiceWeiling Leng0Xinshou Ouyang1Xiaotian Lei2Mingxia Wu3Liu Chen4Qinan Wu5Wuquan Deng6Ziwen Liang7Department of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Internal Medicine, Section of Digestive Diseases, Yale University of Medicine, New Haven, CT 06520, USADepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, ChinaBackground. Our study aimed to observe the effect of sodium glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on diabetic atherosclerosis and investigate the subsequent mechanism. Methods. Aortic atherosclerosis was induced in streptozotocin induced diabetic ApoE−/− mice by feeding with high-fat diet, and dapagliflozin was administrated intragastrically for 12 weeks as treatment. Effects of dapagliflozin on indices of glucose and fat metabolism, IL-1β, IL-18, NLRP3 protein levels, and the reactive oxygen species (ROS) were measured. The atherosclerosis was evaluated by oil red O and hematoxylin-eosin staining. The effects of dapagliflozin on the IL-1β production in culturing primary macrophages of wild type and NLRP3−/− knockout mice were investigated for mechanism analyses. Results. Dapagliflozin treatment showed favorable effects on glucose and fat metabolism, partially reversed the formation of atherosclerosis, inhibited macrophage infiltration, and enhanced the stability of lesion. Also, reduced production of IL-1β, IL-18, NLRP3 protein, and mitochondrial ROS in the aortic tissues was detected with dapagliflozin treatment. In vitro, NLRP3 inflammasome was activated by hyperglucose and hyperlipid through ROS pathway. Conclusions. Dapagliflozin may be of therapeutic potential for diabetic atherosclerosis induced by high-fat diet, and these benefits may depend on the inhibitory effect on the secretion of IL-1β by macrophages via the ROS-NLRP3-caspase-1 pathway.http://dx.doi.org/10.1155/2016/6305735 |
| spellingShingle | Weiling Leng Xinshou Ouyang Xiaotian Lei Mingxia Wu Liu Chen Qinan Wu Wuquan Deng Ziwen Liang The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice Mediators of Inflammation |
| title | The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice |
| title_full | The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice |
| title_fullStr | The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice |
| title_full_unstemmed | The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice |
| title_short | The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice |
| title_sort | sglt 2 inhibitor dapagliflozin has a therapeutic effect on atherosclerosis in diabetic apoe mice |
| url | http://dx.doi.org/10.1155/2016/6305735 |
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