BMC medicine, 2022-09, Vol.20 (1), p.1-309, Article 309
2022
Details
- Autor(en) / Beteiligte
- Titel
- Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling
- Ist Teil von
- BMC medicine, 2022-09, Vol.20 (1), p.1-309, Article 309
- Ort / Verlag
- London: BioMed Central Ltd
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Background Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. Methods A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis). Results The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group. Conclusions Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption. Keywords: Heart failure, Diabetes mellitus, Sodium-glucose cotransporter 2 inhibitor, Left ventricular diastolic function
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1741-7015eISSN: 1741-7015DOI: 10.1186/s12916-022-02485-zTitel-ID: cdi_doaj_primary_oai_doaj_org_article_b641d2ba94b743afbe4d53c71b757333
- Format
- –
- Schlagworte
- Alloxan, Animal models, Attenuation, Care and treatment, Causes of, Complications and side effects, Dapagliflozin, Diabetes, Diabetes mellitus, Disruption, Dosage and administration, Echocardiography, Ejection fraction, Fibrosis, Glucocorticoids, Glucose, Heart failure, Inflammation, Intravenous administration, Kinases, Laboratory animals, Left ventricular diastolic function, Macrophages, Microscopy, Mitochondria, Na+/H+-exchanging ATPase, Prevention, Proteins, Rabbits, Risk factors, Signaling, siRNA, Sodium, Sodium-glucose cotransporter 2 inhibitor, Transfection, Tumor necrosis factor-TNF, Type 2 diabetes, Ultrasonic imaging, Ventricle