Sirtuin 1 activated by SRT1460 protects against myocardial ischemia/reperfusion injury

2021 ◽  
pp. 1-11
Author(s):  
Shanjun Zhao ◽  
Lei Yu
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Sirtuin 1 ◽  
In Vitro Assays ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Infarct Area ◽  
Myocardial Ischemia Reperfusion

BACKGROUND: Ischemia reperfusion usually results in certain degree of damage to the myocardium, which is called myocardial ischemia/reperfusion (I/R) injury. OBJECTIVE: Previous studies have found that Sirt1 plays a critical role in I/R injury by protecting cardiac function. SRT1460 is the activator for Sirt1 that participates in the regulation of various diseases. However, whether SRT1460 has any effects on myocardial I/R injury needs further study. METHODS: The I/R rat model and H/R H9C2 model were established to simulate myocardial I/R injury. The infarct area of the rat heart was examined through TTC staining. The EF and FS of rats were detected through echocardiography. The levels of CK-MB, LDH, MDA, SOD and CK in cardiac tissues, serum or H9C2 cells were measured using commercial kits. Cell viability was assessed through MTT assay. Apoptosis was determined through flow cytometry analysis. Sirt1 expression was measured through western blot. RESULTS: Our work found that SRT1460 reduced the infarct area of the heart induced by myocardial I/R injury. In addition, SRT1460 was confirmed to ameliorate cardiac dysfunction induced by myocardial I/R injury. Further exploration discovered that SRT1460 weakened oxidative stress induced by myocardial I/R injury. Findings from in vitro assays demonstrated that SRT1460 relieved injury of H/R-treated H9C2 cells. Finally, rescue assays proved that Sirt1 knockdown reversed the protective effects of SRT1460 on the injury of H/R-treated H9C2 cells. CONCLUSION: Sirt1 activated by SRT1460 protected against myocardial I/R injury. This discovery may offer new sights on the treatment of myocardial I/R injury.

Ginsenoside Rb1 Inhibits Cardiomyocyte Autophagy via PI3K/Akt/mTOR Signaling Pathway and Reduces Myocardial Ischemia/Reperfusion Injury

2021 ◽  
pp. 1-15
Author(s):  
Guo-Wei Qin ◽  
Pan Lu ◽  
Li Peng ◽  
Wei Jiang
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Ginsenoside Rb1 ◽  
Mtor Signaling Pathway ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardiomyocyte Autophagy ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.

scholarly journals Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenyu Fan ◽  
Liangliang Cai ◽  
Shengnan Wang ◽  
Jing Wang ◽  
Bohua Chen
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Receptor Protein ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Baicalin is a natural flavonoid glycoside that confers protection against myocardial ischemia/reperfusion (I/R) injury. However, its mechanism has not been fully understood. This study focused on elucidating the role of ferroptosis in baicalin-generated protective effects on myocardial ischemia/reperfusion (I/R) injury by using the myocardial I/R rat model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9c2 cells. Our results show that baicalin improved myocardial I/R challenge–induced ST segment elevation, coronary flow (CF), left ventricular systolic pressure , infarct area, and pathological changes and prevented OGD/R-triggered cell viability loss. In addition, enhanced lipid peroxidation and significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal and nuclear receptor coactivator 4 (NCOA4)-medicated ferritinophagy were observed in in vivo and in vitro models, which were reversed by baicalin treatment. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) overexpression compromised baicalin-generated protective effect in H9c2 cells. Taken together, our findings suggest that baicalin prevents against myocardial ischemia/reperfusion injury via suppressing ACSL4-controlled ferroptosis. This study provides a novel target for the prevention of myocardial ischemia/reperfusion injury.

scholarly journals The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xilan Tang ◽  
Jianxun Liu ◽  
Wei Dong ◽  
Peng Li ◽  
Lei Li ◽  
...  
Keyword(s):  
Citric Acid ◽  
Myocardial Ischemia ◽  
Organic Acids ◽  
Reperfusion Injury ◽  
Malic Acid ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components ofFructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. Inin vivorat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation.In vitroexperiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient ofFructus Choerospondiatisresponsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.

Mechanism of decreased adenosine protection in reperfusion injury of aging rats

2000 ◽  
Vol 279 (1) ◽  
pp. H329-H338 ◽  
Author(s):  
Feng Gao ◽  
Theodore A. Christopher ◽  
Bernard L. Lopez ◽  
Eitan Friedman ◽  
Guoping Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
No Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts, administration of adenosine (5 μmol/l) stimulated NO release (1.06 ± 0.19 nmol · min−1 · g−1, P < 0.01 vs. vehicle), increased coronary flow, improved cardiac functional recovery (left ventricular developed pressure 79 ± 3.8 vs. 57 ± 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure development 2,385 ± 103 vs. 1,780 ± 96 in vehicle, P < 0.001), and reduced myocardial creatine kinase loss (95 ± 3.9 vs. 159 ± 4.6 U/100 mg protein, P < 0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced (+0.42 ± 0.12 nmol · min−1 · g−1 vs. vehicle), and the cardioprotective effects of adenosine were also attenuated. Inhibition of NO production in the adult hearts significantly decreased the cardioprotective effects of adenosine, whereas supplementation of NO in the aged hearts significantly enhanced the cardioprotective effects of adenosine. The results show that the protective effects of adenosine on myocardial ischemia-reperfusion injury are markedly diminished in aged animals, and that the loss in NO release in response to adenosine may be at least partially responsible for this age-related alteration.

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