Circ_0001206 regulates miR‐665/CRKL axis to alleviate hypoxia/reoxygenation‐induced cardiomyocyte injury in myocardial infarction

Background: miR-377 is closely related to myocardial regeneration. miR-377-adjusted mesenchymal stem cells abducted ischemic cardiac angiogenesis. Nevertheless, there were rarely reports about the impact of miR-377 on myocardial ischemia injury. The purpose of this work is that whether miR-377 can protect against myocardial injury caused by hypoxia/reoxygenation (H/R). Methods: Gene expression omnibus database ( http://www.ncbi.nlm.nih.gov/geo/ ; no. GSE53211) was utilized to study the differential expression of miR-377 in patients with an acute ST-segment elevation myocardial infarction and healthy controls. The luciferase activity was determined utilizing the dual-luciferase reporter system. Quantitative real-time polymerase chain reaction and Western blotting were used to measure the messenger RNA and protein level. Results: Low expression of miR-377 and high expression of leukocyte immunoglobulin-like receptor B2 (LILRB2) were identified in patients with myocardial infarction from analyzing the Gene Expression Omnibus data set. Besides, miR-377 expression was downregulated in cardiomyocyte exposed to H/R. Additionally, overexpression of miR-377 could visibly improve cardiomyocyte injury by regulating cell activity and apoptosis. Conclusions: In short, our findings suggested that miR-377/LILRB2 might regard as a hopeful therapeutic target for myocardial ischemic.

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Argon Exposure Induces Postconditioning in Myocardial Ischemia–Reperfusion

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248417702891 ◽

2017 ◽

Vol 22 (6) ◽

pp. 564-573 ◽

Cited By ~ 6

Author(s):

Sandrine Lemoine ◽

Katrien Blanchart ◽

Mathieu Souplis ◽

Adrien Lemaitre ◽

Damien Legallois ◽

...

Keyword(s):

Myocardial Infarction ◽

Ischemia Reperfusion ◽

Contractile Force ◽

Left Ventricular ◽

Border Zone ◽

Left Ventricular Ejection ◽

Human Atrial Appendages ◽

Hypoxia Reoxygenation

Background and Purpose: Cardioprotection against ischemia–reperfusion (I/R) damages remains a major concern during prehospital management of acute myocardial infarction. Noble gases have shown beneficial effects in preconditioning studies. Because emergency proceedings in the context of myocardial infarction require postconditioning strategies, we evaluated the effects of argon in such protocols on mammalian cardiac tissue. Experimental Approaches: In rat, cardiac I/R was induced in vivo by transient coronary artery ligature and cardiac functions were evaluated by magnetic resonance imaging. Hypoxia–reoxygenation (H/R)-induced arrhythmias were evaluated in vitro using intracellular microelectrodes on both rat-isolated ventricle and a model of border zone in guinea pig ventricle. Hypoxia–reoxygenation loss of contractile force was assessed in human atrial appendages. In those models, postconditioning was induced by 5 minutes application of argon at the time of reperfusion. Key Results: In the in vivo model, I/R produced left ventricular ejection fraction decrease (24%) and wall motion score increase (36%) which was prevented when argon was applied in postconditioning. In vitro, argon postconditioning abolished H/R-induced arrhythmias such as early after depolarizations, conduction blocks, and reentries. Recovery of contractile force in human atrial appendages after H/R was enhanced in the argon group, increasing from 51% ± 2% in the nonconditioned group to 83% ± 7% in the argon-treated group ( P < .001). This effect of argon was abolished in the presence of wortmannin and PD98059 which inhibit prosurvival phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and MEK/extracellular receptor kinase 1/2 (ERK 1/2), respectively, or in the presence of the mitochondrial permeability transition pore opener atractyloside, suggesting the involvement of the reperfusion injury salvage kinase pathway. Conclusion and Implications: Argon has strong cardioprotective properties when applied in conditions of postconditioning and thus appears as a potential therapeutic tool in I/R situations.

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Downregulated LINC01614 Ameliorates Hypoxia/Reoxygenation-Stimulated Myocardial Injury by Directly Sponging microRNA-138-5p

Dose-Response ◽

10.1177/1559325820913786 ◽

2020 ◽

Vol 18 (1) ◽

pp. 155932582091378 ◽

Cited By ~ 2

Author(s):

Jie Yang ◽

Xue-Song Yang ◽

Qian Zhang ◽

Xin Zhuang ◽

Xiao-Kang Dong ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Ischemia ◽

Ischemia Reperfusion ◽

Myocardial Damage ◽

Gene Expression Omnibus ◽

Cell Counting ◽

Luciferase Reporter ◽

Myocardial Ischemia Reperfusion ◽

Dual Luciferase Reporter Assay ◽

Hypoxia Reoxygenation

Background: LINC01614 was abnormally expressed in myocardial infarction and other heart failures. We attempted to detect the effects of LINC01614 in myocardial ischemia–reperfusion (I/R) injury. Methods: H9c2 cardiomyocyte cells were treated with hypoxia/reoxygenation (H/R) to establish myocardial ischemia (MI) model. Results: Clinical data of Gene Expression Omnibus (GEO) database indicated that LINC01614 was highly regulated in first acute myocardial infarction, whereas miR-138-5p was downregulated in unstable angina pectoris. LINC01614 inhibition promoted cell proliferation and repressed the apoptotic property after H/R treatment using Cell Counting Kit-8 and flow cytometry analysis. Downregulation of LINC01614 enhanced the expression of Bcl-2 but attenuated Bax and cleaved caspase 3 expression after H/R treatment. Bioinformatics prediction and dual-luciferase reporter assay determined that LINC01614 directly targeted miR-138-5p and negatively regulated the expression of miR-138-5p. Furthermore, the overexpression of miR-138-5p significantly strengthened the function of si-LINC01614 in H/R groups. Conclusion: Our results illustrated that reduction in LINC01614 attenuated H/R treatment-induced myocardial damage via sponging miR-138-5p.

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Glucocorticoid Inhibition of Estrogen Regulation of the Serotonin Receptor 2B in Cardiomyocytes Exacerbates Cell Death in Hypoxia/Reoxygenation Injury

Journal of the American Heart Association ◽

10.1161/jaha.120.015868 ◽

2021 ◽

Author(s):

Hemangini A. Dhaibar ◽

Natalie G. Carroll ◽

Shripa Amatya ◽

Lilly Kamberov ◽

Pranshu Khanna ◽

...

Keyword(s):

Myocardial Infarction ◽

Estrogen Receptor ◽

Glucocorticoid Receptor ◽

Serotonin Receptor ◽

Estrogen Receptor Α ◽

Estrogen Regulation ◽

Reoxygenation Injury ◽

Effects Of Stress ◽

Serotonin Receptor 2B ◽

Hypoxia Reoxygenation

Background Stress has emerged as an important risk factor for heart disease in women. Stress levels have been shown to correlate with delayed recovery and increased mortality after a myocardial infarction. Therefore, we sought to investigate if the observed sex‐specific effects of stress in myocardial infarction may be partly attributed to genomic interactions between the female sex hormones, estrogen (E2), and the primary stress hormones glucocorticoids. Methods and Results Genomewide studies show that glucocorticoids inhibit estrogen‐mediated regulation of genes with established roles in cardiomyocyte homeostasis. These include 5‐HT2BR (cardiac serotonin receptor 2B), the expression of which is critical to prevent cardiomyocyte death in the adult heart. Using siRNA, gene expression, and chromatin immunoprecipitation assays, we found that 5‐HT2BR is a primary target of the glucocorticoid receptor and the estrogen receptor α at the level of transcription. The glucocorticoid receptor blocks the recruitment of estrogen receptor α to the promoter of the 5‐HT2BR gene, which may contribute to the adverse effects of stress in the heart of premenopausal women. Using immunoblotting, TUNEL (terminal deoxynucleotidal transferase–mediated biotin–deoxyuridine triphosphate nick‐end labeling), and flow cytometry, we demonstrate that estrogen decreases cardiomyocyte death by a mechanism relying on 5‐HT2BR expression. In vitro and in vivo experiments show that glucocorticoids inhibit estrogen cardioprotection in response to hypoxia/reoxygenation injury and exacerbate the size of the infarct areas in myocardial infarction. Conclusions These results established a novel mechanism underlying the deleterious effects of stress on female cardiac health in the setting of ischemia/reperfusion.

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Hypoxia/Reoxygenation Promotes Myocardial Angiogenesis via anÈNF κ B-dependent Mechanism in a Rat Model of Chronic Myocardial Infarction

Journal of Molecular and Cellular Cardiology ◽

10.1006/jmcc.2000.1299 ◽

2001 ◽

Vol 33 (2) ◽

pp. 283-294 ◽

Cited By ~ 40

Author(s):

Hiroaki Sasaki ◽

Partha S. Ray ◽

Li Zhu ◽

Hajime Otani ◽

Takayuki Asahara ◽

...

Keyword(s):

Myocardial Infarction ◽

Rat Model ◽

Chronic Myocardial Infarction ◽

Dependent Mechanism ◽

Hypoxia Reoxygenation

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Myocardial Ischemia-Reperfusion and Diabetes: Lessons Learned From Bedside to Bench

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.660698 ◽

2021 ◽

Vol 8 ◽

Author(s):

Maya Dia ◽

Alexandre Paccalet ◽

Bruno Pillot ◽

Christelle Leon ◽

Michel Ovize ◽

...

Keyword(s):

Myocardial Infarction ◽

Cell Death ◽

Animal Models ◽

Myocardial Ischemia ◽

Infarct Size ◽

Ischemia Reperfusion ◽

Cardiac Ischemia ◽

Diabetic Patients ◽

Myocardial Ischemia Reperfusion ◽

Hypoxia Reoxygenation

In front of the failure to translate from bench to bedside cardioprotective drugs against myocardial ischemia-reperfusion, research scientists are currently revising their animal models. Owing to its growing incidence nowadays, type 2 diabetes (T2D) represents one of the main risk factors of co-morbidities in myocardial infarction. However, discrepancies exist between reported animal and human studies. Our aim was here to compare the impact of diabetes on cell death after cardiac ischemia-reperfusion in a human cohort of ST-elevation myocardial infarction (STEMI) patients with a diet-induced mouse model of T2D, using a high-fat high-sucrose diet for 16 weeks (HFHSD). Interestingly, a small fraction (<14%) of patients undergoing a myocardial infarct were diabetic, but treated, and did not show a bigger infarct size when compared to non-diabetic patients. On the contrary, HFHSD mice displayed an increased infarct size after an in vivo cardiac ischemia-reperfusion, together with an increased cell death after an in vitro hypoxia-reoxygenation on isolated cardiomyocytes. To mimic the diabetic patients' medication profile, 6 weeks of oral gavage with Metformin was performed in the HFHSD mouse group. Metformin treatment of the HFHSD mice led to a similar extent of lower cell death after hypoxia-reoxygenation as in the standard diet group, compared to the HFHSD cardiomyocytes. Altogether, our data highlight that due to their potential protective effect, anti-diabetic medications should be included in pre-clinical study of cardioprotective approaches. Moreover, since diabetic patients represent only a minor fraction of the STEMI patients, diabetic animal models may not be the most suitable translatable model to humans, unlike aging that appears as a common feature of all infarcted patients.

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Cardioprotective Effects of HO-1-Loaded Collagen-Targeted Phase Change Nanoparticles on Cardiomyocytes Following Acute Myocardial Infarction

Science of Advanced Materials ◽

10.1166/sam.2021.4056 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1685-1690

Author(s):

Shangjun Liu ◽

Wentao Duan ◽

Xiangqun Zhou

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Phase Change ◽

Myocardial Cells ◽

Creatine Kinase Isoenzyme ◽

Acute Mi ◽

Cardioprotective Effects ◽

Change Material ◽

Healthy Participants ◽

Hypoxia Reoxygenation

Acute myocardial infarction (MI) is a major cause of death worldwide. This study utilized collagen-targeted phase change material (PCM) nanoparticles (NPs) to co-encapsulate HO-1 and explored the efficacy of composite PCM NPs on cardiomyocyte progression and development of MI. In this study, we enrolled 32 acute MI patients and 32 healthy participants, and ELISA assay was used to assess the content of creatine kinase isoenzyme (CK-MB). Mice with MI received tail vein administration of HO-1-loaded PCM NPs, followed by RT-qPCR detection of expressions of hypoxia-reoxygenation related genes (SpA, SpB, SpC, Occludin, KGF, and CK18). Patients with acute MI had a higher level of CK-MB. Treatment with HO-1-loaded collagen-targeted PCM NPs decreased expressions of SpA, SpB, SpC, Occludin, KGF, and CK18, facilitating repair of damaged tissues. Of note, NPs loaded with siRNA HO-1 up-regulated the expression of these genes. Collagen-targeted PCM NPs carrying HO-1 effectively promoted the repair of myocardial cells and relieved MI through down-regulation of hypoxia-reoxygenation related genes, which may enhance prevention and treatment for acute MI.

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Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.687501 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lucas Givre ◽

Claire Crola Da Silva ◽

Jon E. Swenson ◽

Jon M. Arnemo ◽

Guillemette Gauquelin-Koch ◽

...

Keyword(s):

Myocardial Infarction ◽

Cell Death ◽

Reperfusion Injury ◽

Ursus Arctos ◽

Cell Injury ◽

Clinical Success ◽

Brown Bear ◽

Optimal Dose ◽

Positive Control ◽

Hypoxia Reoxygenation

Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia–reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 ± 7.06% vs. 79.20 ± 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia–reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.

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