Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure

Gager, Gloria M; Lewinski, Dirk von; Sourij, Harald; Jilma, Bernd; Eyileten, Ceren; Filipiak, K.J.; Hülsmann, Martin; Kubica, Jacek; Postuła, Marek; Siller‐Matula, Jolanta M.

doi:10.1016/j.biopha.2021.112169

Cited by 42 publications

(21 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Those effects were partly mediated by suppressing intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as by decreasing tumor necrosis factor-α (TNF-α) (54,55). Noteworthy, upregulation of these molecules is associated with inflammation (56). However, this is contrary to what has been found in another trial where TNF-α and miR-125b positively correlated (43).…”

Section: Discussionmentioning

confidence: 91%

Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease

Gager

Eyileten

Postuła

et al. 2022

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

BackgroundMicroRNAs (miRNA, miR) have an undeniable physiological and pathophysiological significance and act as promising novel biomarkers. The aim of the study was to investigate blood-derived miRNAs and their association with long-term all-cause mortality in patients with multivessel disease (MVD) suffering from acute coronary syndrome (ACS).Materials and MethodsThis study was an observational prospective study, which included 90 patients with MVD and ACS. Expression of miR-125a, miR-125b, and miR-223 was analysed by polymerase chain reaction (PCR). Patients were followed-up for a median of 7.5 years. All-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events.ResultsElevated expression of miR-125b (>4.6) at the time-point of ACS was associated with increased long-term all-cause mortality (adjusted [adj.] hazard ratio [HR] = 11.26, 95% confidence interval [95% CI]: 1.15–110.38; p = 0.038). The receiver operating characteristic (ROC) analysis showed a satisfactory c-statistics for miR-125b for the prediction of long-term all-cause mortality (area under the curve [AUC] = 0.76, 95% CI: 0.61–0.91; p = 0.034; the negative predictive value of 98%). Kaplan–Meier time to event analysis confirmed an early separation of the survival curves between patients with high vs low expression of miR-125b (p = 0.003). An increased expression of miR-125a and miR-223 was found in patients with non-ST-segment elevation ACS (NSTE-ACS) as compared to those with ST-segment elevation myocardial infarction (STEMI) (p = 0.043 and p = 0.049, respectively) with no difference in the expression of miR-125b between the type of ACS.ConclusionIn this hypothesis generating study, lower values of miR-125b were related to improved long-term survival in patients with ACS and MVD. Larger studies are needed to investigate whether miR-125b can be used as a suitable predictor for long-term all-cause mortality.

show abstract

Section: Discussionmentioning

confidence: 91%

Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease

Gager

Eyileten

Postuła

et al. 2022

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to its effects on diabetes, empagliflozin has also been proven by many studies to possess a variety of anti-inflammatory activities [15][16][17]. On the other hand, empagliflozin has been shown to protect the heart against the damage that can be caused by doxorubicin due to ameliorated ion homeostasis, oxidative stress, and endothelial dysfunction [18]. Empagliflozin, on the other hand, was demonstrated to enhance cardiac function and cardiac remodeling after MI in another research.…”

Section: Resultsmentioning

confidence: 99%

Untitled

2023

J. Med. Chem. Sci.

View full text Add to dashboard Cite

Empagliflozin (EMPA), a selective inhibitor of sodium-glucose cotranspoter2 (SGLT2), mainly regulates blood glucose levels. Many different mechanisms illustrated the significant impact on HD with CVs-outcomes that were unexpected. Specialists have speculated that it could be unrelated to lowering BG levels. The study aims to investigate if empagliflozin has promised a protective effect against the cardiotoxicity induced by doxorubicin in laboratory rats. Male Sprague-Dawley-type rats that did not yet have diabetes were randomly allocated to one of four different groups. The control group was given physiological DW (2 mL), the second group was given EMPA, which was given by oral route at a dose of 10 mg per kg, and the DOXO-group was given cumulatively 15 mg/kg of body weight DOXO, given by IP route at a dose of 2.5 mg per kg. The DOXO and EMPA were administered to the EMPA+DOXO group. Doxorubicin caused cardiotoxicity, which was shown by a significant increase (P< 0.001) in the levels of cTn-1, ICAM-1, and caspase-3. At the same time, the levels of GSH and SOD were significantly reduced-(P <0.001) in the cardiac tissues of rats in the doxorubicin-treated group compared to the control group. The drug also caused Histological changes and lesions. The administration of empagliflozin was found to reduce cardiotoxicity; this can be proved by significant decreases (p~< 0.001) in cTn-1, ICAM-1, and caspase 3 and significant increases (P < 0.001) in SOD and GSH when compared to the DOXO group; and significant improvements (P < 0.001) in the score of CMYO and lesions. In the dosages used in this study, empagliflozin protected the hearts of rats from DOXO-induced cardiotoxicity. This may be related to the interfered^ and ameliorated oxidative stress, the inflammatory response, and the apoptotic pathway.

show abstract

“…(2) The vasodilation function in patients was Disease Markers improved to increase the amount of blood pump. Previous studies have shown that dapagliflozin can reduce the myocardial oxidative stress and inhibit the expression of inflammatory factors like TNF-α, IL-1β, IL-6, and MCP-1 in myocardium by the reduction of malonaldehyde and the increase of superoxide dismutase, thus inhibiting the myocardial hypertrophy and myocardial fibrosis [23][24][25]. (3) Dapagliflozin enables to improve the hemodynamics through osmotic diuresis and improving the arteriosclerosis, thus reducing the cardiac preload and afterload.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dapagliflozin on Indicators of Myocardial Fibrosis and Levels of Inflammatory Factors in Heart Failure Patients

et al. 2022

View full text Add to dashboard Cite

Objective. To explore the effect of dapagliflozin on the myocardial fibrosis and the levels of inflammatory factors in heart failure patients. Methods. 60 patients with T2DM who were diagnosed as acute left heart failure or acute exacerbation of chronic left heart failure in the Department of Cardiology of our hospital from November 1, 2020, to December 31, 2021, during hospitalization were the study subjects. According to the treatment regimen, they were divided into the experimental group (EG) which received dapagliflozin and conventional drugs and the control group (CG) which received conventional drugs, with 30 cases in each group to compare and analyze the clinical indicators such as myocardial fibrosis and inflammatory factors. Results. The levels of TNF-α, IL-1β, IL-6, and hs-CRP in the two groups were decreased gradually after treatment, and the levels of TNF-α, IL-1β, IL-6, and hs-CRP in the EG were visibly lower compared with those in the CG at week 4 of treatment ( P < 0.05 ). The cardiac function evaluation of patients showed that the levels of LVEF and LVEDD in both groups were gradually improved after treatment, with a significant difference from the fourth week. In other words, compared with the CG, the LVEF level in the EG was obviously higher ( P < 0.05 ), the LVEDD level was distinctly lower ( P < 0.05 ), and the levels of ST2, BNP, and MCP-1 in the EG were clearly lower at week 4 of treatment ( P < 0.05 ) with a statistical significance in difference. Conclusion. Dapagliflozin has a definite curative effect in heart failure patients with type 2 diabetes mellitus, which can effectively reduce the inflammatory response of patients and inhibit the myocardial fibrosis, and has a potential value in improving cardiac function and promoting prognosis.

show abstract

Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure

Cited by 42 publications

References 135 publications

Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease

Association Between the Expression of MicroRNA-125b and Survival in Patients With Acute Coronary Syndrome and Coronary Multivessel Disease

Untitled

Effect of Dapagliflozin on Indicators of Myocardial Fibrosis and Levels of Inflammatory Factors in Heart Failure Patients

Contact Info

Product

Resources

About