scholarly journals Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

2018 ◽  
Vol 49 (4) ◽  
pp. 1476-1491 ◽  
Author(s):  
Shu-Bo  Zhang ◽  
Tie-Jun Liu ◽  
Guo-Hua Pu ◽  
Bao-Yong Li ◽  
Xiao-Zeng Gao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Myocardial Cells ◽  
Non Coding Rna ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion ◽  
Pka Pathway ◽  
Long Non Coding Rna

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

TNF-α antagonism ameliorates myocardial ischemia-reperfusion injury in mice by upregulating adiponectin

2015 ◽  
Vol 308 (12) ◽  
pp. H1583-H1591 ◽  
Author(s):  
Chao Gao ◽  
Yi Liu ◽  
Qiujun Yu ◽  
Qiang Yang ◽  
Bing Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Globular Domain ◽  
Male Adult ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion ◽  
Factor Α

Tumor necrosis factor-α (TNF-α) antagonism alleviates myocardial ischemia-reperfusion (MI/R) injury. However, the mechanisms by which the downstream mediators of TNF-α change after acute antagonism during MI/R remain unclear. Adiponectin (APN) exerts anti-ischemic effects, but it is downregulated during MI/R. This study was conducted to investigate whether TNF-α is responsible for the decrease of APN, and whether antagonizing TNF-α affects MI/R injury by increasing APN. Male adult wild-type (WT), APN knockout (APN KO) mice, and those with cardiac knockdowns of APN receptors via siRNA injection were subjected to 30 min of MI followed by reperfusion. The TNF-α antagonist etanercept or globular domain of APN (gAD) was injected 10 min before reperfusion. Etanercept ameliorated MI/R injury in WT mice as evidenced by improved cardiac function, and reduced infarct size and cardiomyocyte apoptosis. APN concentrations were augmented in response to etanercept, followed by an increase in AMP-activated protein kinase phosphorylation. Etanercept still increased cardiac function and reduced infarct size and apoptosis in both APN KO and APN receptors knockdown mice. However, its potential was significantly weakened in these mice compared with the WT mice. TNF-α is responsible for the decrease in APN during MI/R. The cardioprotective effects of TNF-α neutralization are partially due to the upregulation of APN. The results provide more insight into the TNF-α-mediated signaling effects during MI/R and support the need for clinical trials to validate the efficacy of acute TNF-α antagonism in the treatment of MI/R injury.

scholarly journals Effects on cardiac function, remodeling and inflammation following myocardial ischemia–reperfusion injury or unreperfused myocardial infarction in hypercholesterolemic APOE*3-Leiden mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Niek J. Pluijmert ◽  
Cindy I. Bart ◽  
Wilhelmina H. Bax ◽  
Paul H. A. Quax ◽  
Douwe E. Atsma
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trials ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Apo E ◽  
Lv Remodeling ◽  
Myocardial Ischemia Reperfusion

Abstract Many novel therapies to treat myocardial infarction (MI), yielding promising results in animal models, nowadays failed in clinical trials for several reasons. The most used animal MI model is based on permanent ligation of the left anterior descending (LAD) coronary artery in healthy mice resulting in transmural MI, while in clinical practice reperfusion is usually accomplished by primary percutaneous coronary interventions (PCI) limiting myocardial damage and inducing myocardial ischemia–reperfusion (MI-R) injury. To evaluate a more similar murine MI model we compared MI-R injury to unreperfused MI in hypercholesterolemic apolipoprotein (APO)E*3-Leiden mice regarding effects on cardiac function, left ventricular (LV) remodeling and inflammation. Both MI-R and MI resulted in significant LV dilation and impaired cardiac function after 3 weeks. Although LV dilation, displayed by end-diastolic (EDV) and end-systolic volumes (ESV), and infarct size (IS) were restricted following MI-R compared to MI (respectively by 27.6% for EDV, 39.5% ESV, 36.0% IS), cardiac function was not preserved. LV-wall thinning was limited with non-transmural LV fibrosis in the MI-R group (66.7%). Two days after inducing myocardial ischemia, local leucocyte infiltration in the infarct area was decreased following MI-R compared to MI (36.6%), whereas systemic circulating monocytes were increased in both groups compared to sham (130.0% following MI-R and 120.0% after MI). Both MI-R and MI models against the background of a hypercholesterolemic phenotype appear validated experimental models, however reduced infarct size, restricted LV remodeling as well as a different distributed inflammatory response following MI-R resemble the contemporary clinical outcome regarding primary PCI more accurately which potentially provides better predictive value of experimental therapies in successive clinical trials.

scholarly journals LncRNA LINC00461 exacerbates myocardial ischemia-reperfusion injury via microRNA-185-3p/Myd88

2021 ◽  
Author(s):  
Feng Gao ◽  
Xiaochen Wang ◽  
Tingting Fan ◽  
Zhidan Luo ◽  
Mengqin Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Primary Response ◽  
Cardiomyocyte Apoptosis ◽  
Non Coding Rna ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Objective Long non-coding RNA (lncRNA) play critically in myocardial ischemia-reperfusion (I/R) injury. Thus, it was proposed to investigate the mechanism of LINC00461 in the disease through mediating microRNA-185-3p (miR-185-3p)/myeloid differentiation primary response gene 88 (Myd88) axis. Methods Mice with I/R injury were injected with the vectors that altered miR-185-3p and LINC00461 expression. miR-185-3p, LINC00461 and Myd88 expression in mice with I/R injury were measured, as well as cardiac function, hemodynamics, myocardial fibrosis, infarction area, oxidative stress, and cardiomyocyte apoptosis. Results Raised LINC00461 and Myd88 and suppressed miR-185-3p levels were measured in I/R mice. Down-regulating LINC00461 or up-regulating miR-185-3p recovered cardiac function, reduced myocardial collagen hyperplasia, fibrosis and infarction, and attenuated oxidative stress and cardiomyocyte apoptosis in mice with I/R. Conclusion Down-regulation of LINC00461 attenuates myocardial I/R injury via suppressing miR-185-3p-targeted Myd88 expression.

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