Identification of Novel Molecular Network Expression in Acute Myocardial Infarction

Matboli, Marwa; Shafei, Ayman; Agwa, Sara Hassan; Elzahy, Sherif Sammir; Anwar, Ahmed K.; Mansour, Amr R.; Gaber, Ahmed I.; Said, Ali E.A.; Lwis, Paula; Hamdy, Marwa

doi:10.2174/1389202920666190820142043

Cited by 6 publications

(3 citation statements)

References 37 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The underlying mechanisms might be related to the activation of PGAM5-Drp1 axis, The inevitable cardiac remodeling post MI causes cardiac dysfunction easily, triggering HF and sudden cardiac death, leading to a high mortality rate. 32,33 Recently, several large and powerful RCTs indicated that SGLT2i could decrease the risk of worsening HF or cardiac death in HF patients without diabetes. [13][14][15] Accordingly, SGLT2i were strongly recommended as a routine medical therapy for HF in the latest AHA/ACC guidelines, especially for these patients with HFrEF (Ia).…”

Section: Discussionmentioning

confidence: 99%

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

Fan¹,

Xu²,

Chen³

et al. 2022

DDDT

View full text Add to dashboard Cite

Dapagliflozin (DAPA) has been reported to have significant cardiac protective effects on heart failure (HF). However, the dose and time, as well as the underlying mechanisms, for DAPA treatment in acute myocardial infarction (AMI) remain controversial. The aim of this study aimed to assess the efficacy and safety of DAPA treatment along with an increased concentration gradient for AMI and explore the potential mechanisms. Methods: Non-diabetic Sprague-Dawley rats were used for establishing AMI models and then were treated with three different concentrations of DAPA [0.5 mg/kg, 1 mg/kg and 1.5 mg/kg, described as AMI+DAPA Low, AMI+DAPA Medium (Med) and AMI +DAPA High, respectively] for six weeks from the onsetting of AMI. Echocardiography, histological staining and Western blot were performed to assess the relevant cardiac protective effects. Mitochondrial biogenesis and myocardial apoptosis were evaluated via the electron microscopy and TUNEL assay, respectively, as well as the Immunoblotting. In vitro, H9c2 cells were subjected to hypoxic treatment to assess the efficacy of DAPA on mitochondrial biogenesis and apoptosis. Results: The medium dose of DAPA treatment could significantly reduce the infarct size (P < 0.01) and the echocardiography results showed that the MI-induced damage in cardiac function got partly repaired, showing no significant difference in left ventricle ejection fraction (LVEF) versus the Sham group (Sham vs AMI+DAPA Med group: 70.47% vs 61.73%). The Western blotting results confirmed the relevant benefits and the underlying mechanisms might be through the activation of PGAM5/Drp1 signaling pathway to normalize the mitochondrial fission and reduce cardiomyocyte apoptosis. Moreover, a medium dose of DAPA treatment could avoid increased damage to the bladder endothelium following higher treatment doses. Conclusion: Appropriate dose of DAPA treatment could improve the cardiac remodeling and reduce the cardiomyocyte apoptosis after AMI, without increased damage to bladder endothelium, which might be more preferred for MI patients without diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Fan¹,

Xu²,

Chen³

et al. 2022

DDDT

View full text Add to dashboard Cite

show abstract

“…Myocardial infarction causes cardiac dysfunction and adverse cardiac remodeling, leading to high morbidity and mortality rates [16]. A recent study revealed that DAPA exerts a cardioprotective role in patients without diabetes mellitus [8].…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Improves Cardiac Function, Remodeling, Myocardial Apoptosis, and Inflammatory Cytokines in Mice with Myocardial Infarction

Wang

Yan

et al. 2021

J. of Cardiovasc. Trans. Res.

View full text Add to dashboard Cite

Dapagliflozin (DAPA) exerts cardioprotective effects in non-diabetic patients. Nonetheless, the protective mechanism remains unknown. This study aims to evaluate the performance of DAPA on cardiac function and remodeling as well as its potential mechanism in mice with myocardial infarction (MI). Here, a MI mice model was established. One week after MI, mice were treated with saline or DAPA (1.5 mg/kg/day) for 4 weeks. At the end of this study, echocardiography was performed to assess cardiac structure and function. Myocardial apoptosis was analyzed by Western blot and immunofluorescence. Inflammatory cytokines and cardiac fibrosis were analyzed by real-time PCR and Masson's trichrome stain, respectively. Results showed that DAPA improved cardiac structure and function, attenuated cardiac fibrosis, and inhibited inflammatory cytokines and myocardial apoptosis. Moreover, the inhibition of PI3K/AKT/mTOR pathway might be related to the cardioprotective role of DAPA. These findings reveal that dapagliflozin is a potential therapeutic agent for MI patients without diabetes.

show abstract

“…In the early stages of fibrosis, MMP-9 is the major enzyme causing ECM decomposition, which can lead to ECM degeneration, a disorder of myocardial arrangement and abnormal systolic function ( Wu et al, 2018 ). Studies have found that sustained activation of β-adrenoceptors leads to an increase in the synthesis and secretion of fibrillar collagen types I and III and finally to pathological MF ( Matboli et al, 2019 ). Our present data showed the concentration of TGF-β markedly increased in the ISO group comparing to the CON group.…”

Section: Discussionmentioning

confidence: 99%

8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

Xue

Liu

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.

show abstract

Identification of Novel Molecular Network Expression in Acute Myocardial Infarction

Cited by 6 publications

References 37 publications

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

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

Dapagliflozin Improves Cardiac Function, Remodeling, Myocardial Apoptosis, and Inflammatory Cytokines in Mice with Myocardial Infarction

8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway

Contact Info

Product

Resources

About