Appropriate Dose of Dapagliflozin Improves Cardiac Outcomes by Normalizing Mitochondrial Fission and Reducing Cardiomyocyte Apoptosis After Acute Myocardial Infarction

Fan, Zhong-guo; Xu, Yang; Chen, Xi; Ji, Ming-yue; Ma, Genshan

doi:10.2147/dddt.s371506

Cited by 16 publications

(14 citation statements)

References 48 publications

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“…Long-standing diabetes may cause several complications including diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, and macrovascular complications. These complications may have an adverse impact on the quality of life of the diabetic population and result in elevated morbidity and mortality [39].…”

Section: Resultsmentioning

confidence: 99%

Drug Utilization Evaluation of Antidiabetic Agents in Primary Care Clinics of a South Indian Rural Province

Theivasigamani¹,

Palaniappan²

2022

Int J Pharm Res Allied Sci

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A cross-sectional study was conducted to analyze the utilization of antidiabetic agents among patients with Type-2 Diabetes Mellitus in primary care clinics of a South Indian rural province of Erode district, Tamilnadu, India. The study was conducted for a period of one year using a structured validated questionnaire. There was a total of 487 diabetic patients residing in the rural area of a south Indian state were included in this drug utilization evaluation. Majority of the diabetic patients in this study were female (n= 279; 57.28%), married (n=463; 95%), unemployed (n=272; 55.85%), and illiterate (n=180; 36.96%), between the age of 51-60 years (175; 35.93%), and has past medical history of T2DM (n=328; 67.35%). All of them were diagnosed with T2DM (n=487; 100%). The majority of the diabetes patients were receiving oral hypoglycemic agents (OHA) (n=433; 88.91%), among these, 125 (25.66%) were treated with a single anti-diabetic agent as monotherapy, 208 (42.71%) were treated with twodrug regimens, and 136 (27.92%) were treated with three-drug regimens. There was an increasing trend of diabetes among the rural population. It was mainly due to their inappropriate lifestyle habits and lack of awareness of diabetes and its complications among the poor general population of this district. Polypharmacy was commonly seen among diabetes patients and the majority were receiving more than 2 antidiabetic medications. A well-structured health interventional program is warranted to reduce the increasing trend of diabetes and to reduce negative health outcomes.

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Section: Resultsmentioning

confidence: 99%

Drug Utilization Evaluation of Antidiabetic Agents in Primary Care Clinics of a South Indian Rural Province

Theivasigamani¹,

Palaniappan²

2022

Int J Pharm Res Allied Sci

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“…A meta‐analysis of these preclinical investigations found that SGLT2 inhibitors decrease myocardial infarct size, independent of T2DM 30 . Dapagliflozin has been found to ameliorate cardiac function, remodelling, myocardial apoptosis, and inflammatory cytokines, normalize mitochondrial fission, and modulate macrophage polarization via STAT3 signalling in MI 31–33 . Empagliflozin directly impedes the Na + /H + exchanger 1 in cardiomyocytes to suppress autophagic cell death in MI mice 34 .…”

Section: Discussionmentioning

confidence: 99%

“…30 Dapagliflozin has been found to ameliorate cardiac function, remodelling, myocardial apoptosis, and inflammatory cytokines, normalize mitochondrial fission, and modulate macrophage polarization via STAT3 signalling in MI. [31][32][33] Empagliflozin directly impedes the Na + /H + exchanger 1 in cardiomyocytes to suppress autophagic cell death in MI mice. 34 Moreover, SGLT2 inhibitors alleviate reperfusion injury, [35][36][37] boost endothelial function, orchestrate myocardial energy metabolism, and attenuate oxidative stress pathways to augment coronary blood flow.…”

Section: Grade Of Evidencementioning

confidence: 99%

Effect of sodium‐glucose cotransporter‐2 inhibitors on myocardial infarction incidence: A systematic review and meta‐analysis of randomized controlled trials and cohort studies

Huang,

Dannya,

Liu

et al. 2023

Diabetes Obesity Metabolism

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AimTo assess whether sodium‐glucose cotransporter‐2 (SGLT2) inhibitors reduce myocardial infarction (MI) incidence in patients with or without type 2 diabetes.MethodsPubMed, Embase, Web of Science, the Cochrane library, and https://ClinicalTrials.gov were searched up to 7 May 2022. Randomized controlled trials (RCTs) and cohort studies reporting the effects of SGLT2 inhibitor treatment on MI incidence were included. Relative risks (RRs) with a 95% confidence interval (CI) for MI incidence were extracted and pooled. Subgroup analysis and meta‐regression were performed to explore the heterogeneity.ResultsThis meta‐analysis included 54 RCTs and 32 cohort studies, with data from six SGLT2 inhibitors and 3 394 423 individuals. In the overall analysis, SGLT2 inhibitors significantly reduced MI incidence in RCTs (RR 0.9, 95% CI 0.84–0.96) and cohort studies (RR 0.89, 95% CI 0.83–0.94). In RCTs, the results of the subgroup analysis revealed no significant alterations in outcomes based on different SGLT2 inhibitor types, control drug types, cardiovascular disease (CVD) status and sources of outcome extraction (p for interaction >0.05). In cohort studies, the presence or absence of CVD led to similar effects of SGLT2 inhibitors on decreasing MI incidence (p for interaction = 0.179). However, variations in results were observed based on the type of control group in cohort studies (p for interaction = 0.036). Meta‐regression results did not reveal an association between baseline cardiovascular risk factors, follow‐up length, or MI incidence.ConclusionsIn both RCTs and cohort studies, SGLT2 inhibitors reduced MI incidence. The cardioprotective effects of SGLT2 inhibitors were observed in patients with and without a history of CVD.

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“…Various approaches such as pharmacologic interventions and stem cell therapy have been shown to attenuate AVR after AMI. 10,11 Cell transplantation is a new therapeutic option for AMI and has attracted increasing interest from scholars. 12 The easy availability of large quantities makes bone marrow-derived mononuclear cells reliable and attractive donor cells.…”

Section: Introductionmentioning

confidence: 99%

“…Various approaches such as pharmacologic interventions and stem cell therapy have been shown to attenuate AVR after AMI. 10,11…”

Section: Introductionmentioning

confidence: 99%

SGLT2 inhibitor-pretreated macrophage transplantation improves adverse ventricular remodeling after acute myocardial infarction

Chen

Zhang

Zhou

et al. 2023

Journal of Cardiovascular Pharmacology

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Macrophages play an important role in the progression of acute myocardial infarction (AMI). Studies have shown that sodium-dependent glucose transporter 2 inhibitor (SGLT2i) after AMI could increase the proportion of M2 type/M1 macrophages and reduces adverse ventricular remodeling (AVR) post AMI. This study aimed to investigate whether SGLT2i-pretreated macrophage transplantation could reduce AVR after AMI and the underlying mechanisms. C57BL/6 mice were used to establish an AMI model by ligating the coronary arteries. Dynamic observation of transplanted bone marrow-derived macrophages (BMDMs) was performed using an in vivo imaging system (IVIS). Cardiac function was assessed using echocardiography. The fibrosis ratio was measured using Masson’s trichrome staining. Cardiomyocyte apoptosis was measured using the TUNEL assay. Macrophage subtypes were measured using flow cytometry. We detected the expression of inflammatory factors in the myocardium and serum using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). IVIS revealed that transplanted SGLT2i-pretreated BMDMs were present in the infarcted myocardium for 7 d. Flow cytometry revealed that SGLT2i-pretreated BMDMs promoted the conversion of native-derived macrophages to the M2-type. SGLT2i-pretreated BMDMs also reduced inflammatory factors (IL-6, TNFα, and IL-1β) in the infarcted myocardium and serum. At 28 d post-AMI, SGLT2i-pretreated BMDMs increased cardiac function and vascular density, but reduced cardiomyocyte hypertrophy. SGLT2i-pretreated BMDMs could reduce cardiomyocyte apoptosis and fibrotic area ratio. In conclusion, transplanted SGLT2i-pretreated BMDMs were present in the infarcted myocardium for 7 d and improved AVR by reducing inflammation and modulating the conversion of native mice-derived macrophages to M2-type macrophages.

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Appropriate Dose of Dapagliflozin Improves Cardiac Outcomes by Normalizing Mitochondrial Fission and Reducing Cardiomyocyte Apoptosis After Acute Myocardial Infarction

Cited by 16 publications

References 48 publications

Drug Utilization Evaluation of Antidiabetic Agents in Primary Care Clinics of a South Indian Rural Province

Drug Utilization Evaluation of Antidiabetic Agents in Primary Care Clinics of a South Indian Rural Province

Effect of sodium‐glucose cotransporter‐2 inhibitors on myocardial infarction incidence: A systematic review and meta‐analysis of randomized controlled trials and cohort studies

SGLT2 inhibitor-pretreated macrophage transplantation improves adverse ventricular remodeling after acute myocardial infarction

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