scholarly journals Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

2016 ◽  
Vol 39 (3) ◽  
pp. 1021-1030 ◽  
Author(s):  
YaBei Zuo ◽  
YuZhao Wang ◽  
HaiJuan Hu ◽  
Wei Cui
Keyword(s):  
Western Blot ◽  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mrna Level ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Rt Pcr ◽  
Myocardial Ischemia Reperfusion ◽  
Gsk 3Β

Objective: This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Method: Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Results: Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. Conclusion: These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.

Zingerone Alleviates Myocardial Ischemia/Reperfusion Injury

2021 ◽  
Vol 19 (4) ◽  
pp. 543-549
Author(s):  
Fanglin Luo ◽  
Shunxiang Luo ◽  
Yanqing Wu
Keyword(s):  
Myocardial Infarction ◽  
Proinflammatory Cytokine ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Cytokine Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Using a rat model, we have explored the underlying mechanism of ischemia/reperfusion (I/R)-mediated myocardial infarction and assessed the protective potential of zingerone. The results show that zingerone exhibits not only the myocardial protective effect, but also antioxidative and anti-inflammatory effects by suppression of markers of oxidation and proinflammatory cytokine release. Zingerone promotes protective effects against I/R-induced myocardial infarction by regulating Nrf2/HO-1 and NF-κB signaling pathways. These findings provide novel insights into the effects of zingerone on the cardioprotective mechanism of myocardial injury after I/R and may open new avenues for myocardial infarction treatment.

Abstract 423: Proteasome Priming by Protein Kinase G Protects Against Myocardial Ischemia-reperfusion Injury

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xuejun Wang ◽  
Erin J Terpstra ◽  
Eduardo Callegari ◽  
Chengjun Hu ◽  
Hanming Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
26S Proteasome ◽  
Transgenic Mouse Line ◽  
Pde5 Inhibition ◽  
Myocardial Ischemia Reperfusion

Cardiac proteasome functional insufficiency is implicated in a large subset of heart disease and has been experimentally demonstrated to play an essential role in cardiac proteotoxicity, including desmin-related cardiomyopathy and myocardial ischemia-reperfusion (I-R) injury. Pharmacological inhibition of phosphodiesterase 5 (PDE5) via sildenafil for example, which can stabilize cGMP and thereby increase cGMP-dependent protein kinase (PKG) activity, is consistently reported to protect against I-R injury; however, the underlying mechanism is not fully understood. We have recently discovered that PKG activation enhances proteasomal degradation of misfolded proteins (Ranek, et al. Circulation 2013), prompting us to hypothesize that proteasome-priming may contribute to cardioprotection-induced by PDE5 inhibition. Here we used a cardiomyocyte-restricted proteasome inhibition transgenic mouse line (Tg) and non-Tg (Ntg) littermates to interrogate the action of sildenafil on I-R injury created by left anterior descending artery (LAD) ligation (30 min) and release (24 hr). Sildenafil was administered 30 min before LAD ligation. Results showed that (1) the 26S proteasome activity of the Ntg I-R hearts was significantly elevated by sildenafil but this elevation was blocked in the Tg line; (2) the infarct size reduction by sildenafil treatment in Ntg mice was completely abolished in the Tg mice with the same treatment; and (3) systolic and diastolic function impairment after I/R was markedly attenuated in sildenafil-treated Ntg mice, but not in the sildenafil-treated Tg mice. Additionally, immunoprecipitation assays show that PKG interacted with the proteasome in cultured cardiomyocytes, and this interaction appeared to be augmented by sildenafil treatment. Moreover, in vitro incubation of active PKG with purified human 26S proteasomes increased proteasome peptidase activities and the phosphorylation at specific serine residues of a 19S proteasome subunit as revealed by “gel-free” nano-LC-MS/MS. We conclude that active PKG directly interacts with, phosphorylates, and increases the activities of, the proteasome and that proteasome priming mediates to cardioprotection of PDE5 inhibition against I-R injury.

scholarly journals The Protective Effect of Total Flavones from Rhododendron simsii Planch. on Myocardial Ischemia/Reperfusion Injury and Its Underlying Mechanism

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sheng-Yong Luo ◽  
Qing-Hua Xu ◽  
Gong Peng ◽  
Zhi-Wu Chen
Keyword(s):  
Myocardial Infarction ◽  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Assay Method ◽  
Protective Effects ◽  
Rhododendron Simsii ◽  
Rhoa Activity ◽  
Protein Expressions

Objectives. Total flavones from Rhododendron simsii Planch. (TFR) are the effective part extracted from the flowers of Rhododendron simsii Planch. and have obvious protective effects against cerebral ischemic or myocardial injuries in rabbits and rats. However, their mechanism of cardioprotection is still unrevealed. Therefore, the present study was designed to investigate the effect of TFR on myocardial I/R injury and the underlying mechanism. Methods. TFR groups were treated by gavage once a day for 3 days at a dose of 20, 40, and 80 mg/kg, respectively, and then the model of myocardial I/R injury was established. Myocardial infarction, ST-segment elevation, and the expression of UTR, ROCK1, ROCK2, and p-MLC protein in rat myocardium were determined at 90 min after reperfusion. UTR siRNA in vivo transfection and competition binding assay method were used to study the relationship between the protective effect of TFR and UTR. Results. The expression of UTR protein markedly decreased in myocardium of UTR siRNA transfection group rats. TFR could significantly reduce the infarct size and inhibit the increase of RhoA activity and ROCK1, ROCK2, and p-MLC protein expressions both in WT and UTR knockdown rats. The reducing rate of TFR in myocardial infarction area, RhoA activity, and ROCK1, ROCK2, and p-MLC protein expressions in UTR knockdown rats decreased markedly compared with that in WT rats. In addition, TFR had no obvious effect on the increase of ΣST in UTR knockdown rats in comparison with that in model group. In particular, TFR could significantly inhibit the combination of [I125]-hu-II and UTR, and IC50 was 0.854 mg/l. Conclusions. The results indicate that the protective effect of TFR on I/R injury may be correlated with its blocking UTR and the subsequent inhibition of RhoA/ROCK signaling pathway.

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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