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Effects of Sodium Glucose Cotransporter 2 Inhibitors on Left Ventricular Diastolic Function in a Diabetic Rabbit Model

Other Titles
 토끼 당뇨모델에서 Sodium Glucose Cotransporter 2 억제제가 좌심실 이완기능에 미치는 영향 
Authors
 김다래 
College
 College of Medicine (의과대학) 
Department
 Dept. of Internal Medicine (내과학교실) 
Degree
박사
Issue Date
2017
Abstract
Sodium glucose cotransporter 2 (SGLT2) inhibitors represent a new class of diabetic medications. A recent trial reported that SGLT2 inhibitors reduce mortality and heart failure hospitalization in diabetic patients. However, mechanisms of the cardiovascular protective effects of SGLT2 inhibitors are not known. Considering that approximately 80% of diabetic patients have heart failure with preserved ejection fraction (EF), SGTL2 inhibitors might have beneficial effects on the diastolic function of the left ventricle (LV). In this study, we investigated whether targeting SGLT2 improves left ventricular diastolic function in a diabetic rabbit model. In addition, we sought to determine if SGLT2 inhibitors reduce cardiac fibrosis by reducing profibrotic signaling protein expression. Thirty male New Zealand rabbits were classified into 3 groups. Group 1 consisted of normal rabbits. Group 2 consisted of diabetic rabbits, while group 3 consisted of diabetic rabbits treated with SGLT2 inhibitor, dapagliflozin, for 8 weeks. At 8 weeks of follow-up, conventional echocardiography with speckle tracking analysis was performed. At the end of the experiments, all rabbits were sacrificed for immunohistochemistry staining. At the 8 week follow-up, blood fasting glucose was significantly higher in group 2 compared to groups 1 and 3. LV systolic parameters (LV ejection fraction and LV fractional shortening) and cardiac chamber sizes did not differ among the three groups. However, LV diastolic function, reflected by septal and lateral e’ velocity, was significantly lower in group 2 compared to groups 1 and 3. LV global longitudinal strain was significantly lower and LV global circumferential strain was significantly higher in group 2 compared to groups 1 and 3. Group 2 revealed significantly increased cardiac fibrosis, which was accompanied by increased expression of the profibrotic proteins serum and glucocorticoid-regulated kinase 1 (SGK1) and epithelial sodium channel (ENaC). However, in group 3, fibrosis and profibrotic protein expression was significantly lower than in group 2. Dapagliflozin attenuated LV diastolic dysfunction and subclinical LV systolic dysfunction, reflected by e’ velocity and LV global longitudinal strain respectively. These findings suggest that dapagliflozin reduces the development of cardiac fibrosis and expression of the profibrotic proteins, SGK1 and ENaC, in a diabetic rabbit model.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 3. Dissertation
Yonsei Authors
Kim, Da Rae(김다래)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175070
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