scholarly journals Growth Hormone Secretagogues and the Regulation of Calcium Signaling in Muscle

2019 ◽  
Vol 20 (18) ◽  
pp. 4361 ◽  
Author(s):  
Elena Bresciani ◽  
Laura Rizzi ◽  
Silvia Coco ◽  
Laura Molteni ◽  
Ramona Meanti ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
Growth Hormone Secretagogues ◽  
Amino Acid Peptide ◽  
Pathological Conditions ◽  
Muscle Impairment

Growth hormone secretagogues (GHS) are a family of synthetic molecules, first discovered in the late 1970s for their ability to stimulate growth hormone (GH) release. Many effects of GHS are mediated by binding to GHS-R1a, the receptor for the endogenous hormone ghrelin, a 28-amino acid peptide isolated from the stomach. Besides endocrine functions, both ghrelin and GHS are endowed with some relevant extraendocrine properties, including stimulation of food intake, anticonvulsant and anti-inflammatory effects, and protection of muscle tissue in different pathological conditions. In particular, ghrelin and GHS inhibit cardiomyocyte and endothelial cell apoptosis and improve cardiac left ventricular function during ischemia–reperfusion injury. Moreover, in a model of cisplatin-induced cachexia, GHS protect skeletal muscle from mitochondrial damage and improve lean mass recovery. Most of these effects are mediated by GHS ability to preserve intracellular Ca2+ homeostasis. In this review, we address the muscle-specific protective effects of GHS mediated by Ca2+ regulation, but also highlight recent findings of their therapeutic potential in pathological conditions characterized by skeletal or cardiac muscle impairment.

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.

scholarly journals Inhibition of Myocardial Ischemia/Reperfusion Injury by Exosomes Secreted from Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Heng Zhang ◽  
Meng Xiang ◽  
Dan Meng ◽  
Ning Sun ◽  
Sifeng Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricle ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Area At Risk

Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine. In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia/reperfusion injury based on the reports published between January 2000 and September 2015 and indexed in the PUBMED and Web of Science databases. The effect of exosomes on heart function was evaluated according to the following parameters: the area at risk as a percentage of the left ventricle, infarct size as a percentage of the area at risk, infarct size as a percentage of the left ventricle, left ventricular ejection fraction, left ventricular fraction shortening, end-diastolic volume, and end-systolic volume. Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function. However, further mechanistic studies, therapeutic safety, and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury.

Hyperthermia-Induced Cardioprotection Is Potentiated by Ischemic Postconditioning in Rats

2009 ◽  
Vol 234 (5) ◽  
pp. 573-581 ◽  
Author(s):  
Yukichi Murozono ◽  
Naohiko Takahashi ◽  
Tetsuji Shinohara ◽  
Tatsuhiko Ooie ◽  
Yasushi Teshima ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Ischemic Postconditioning ◽  
Initial Moment ◽  
Protective Effects ◽  
Perfused Heart ◽  
Ventricular Performance ◽  
Akt Phosphorylation

We tested the hypothesis that the protective effects of hyperthermia (HT) could be augmented by ischemic postconditioning (PostC) via enhancement of reperfusion-induced Akt phosphorylation. The role of the mitoKATP channel as an effecter to protect hearts against ischemia/reperfusion injury was also investigated. In isolated perfused heart experiments using a Langendorff apparatus, 30 min of no-flow global ischemia was followed by 120 min of reperfusion. Ischemic PostC, 5 cycles of 10-sec reperfusion/10-sec ischemia, was achieved at the initial moment of reperfusion. Hyperthermia (HT, 43°C for 20 min) was applied 24 hr before ischemia onset. Ischemic PostC alone did not show significant protection, but HT did. The HT-induced protection in terms of infarct size, recovery of left ventricular performance, amount of released creatine kinase and apoptosis were enhanced by ischemic PostC. These protective effects were consistent with the levels of Akt phosphorylation 7 min after reperfusion and were completely blocked by the pretreatment with the phosphatidylinositol 3-kinase inhibitor wortmannin. HT-induced protection was also completely abolished by concomitant perfusion with 5-hydroxydecanoate (5HD, 100 μM), an inhibitor of the mitochondrial ATP-sensitive potassium (mitoKATP) channel. However, the potentiated protection by ischemic PostC remained, even in the presence of 5HD. In conclusion, ischemic PostC could potentiate the protective effects of HT possibly via enhancement of reperfusion-induced Akt phosphorylation. Although the opening of the mitoKATP channel is predominantly involved as an effecter in HT-induced protection, potentiated protection by ischemic PostC may involve mechanisms other than the mitoKATP channel.

Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72

2000 ◽  
Vol 279 (2) ◽  
pp. H836-H843 ◽  
Author(s):  
Guro Valen ◽  
Tsutomu Kawakami ◽  
Peeter Tähepôld ◽  
Alexandra Dumitrescu ◽  
Christian Löwbeer ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Posttranscriptional Regulation ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Acute Administration ◽  
Protective Effects ◽  
Heat Shock Protein 72

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion ( n = 6–11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone ( n = 7–8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.

P2687Impact of cardiovascular risk factors on effectiveness of remote ischemic preconditioning in the setting of ischemia/reperfusion-injury in a langendorff heart model

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Hidalgo Pareja ◽  
J M Muessig ◽  
A M Nia ◽  
M Masyuk ◽  
M Kelm ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Elderly Patients ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ventricular Volume ◽  
Left Ventricular ◽  
Protective Effects ◽  
Heart Model

Abstract Introduction Cardiovascular diseases are the most frequent cause of death in the western world. During myocardial infarction both, ischemia and reperfusion after therapeutic intervention cause myocardial damages, resulting in ischemia/reperfusion-injury (I/R-injury). Research therefore searches cardio protective interventions, aiming to reduce myocardial injury and following consequences such as heart failure. A promising method, named Remote Ischemic Preconditioning (RIPC), consists of transient local ischemia distant from the heart. Its cardio-protective effects were already proved in basic research but failed in clinical trials. Purpose The aim of the study is to examine the impact of cardiac risk factors like diabetes mellitus (DM) or age on effectiveness of RIPC in order to identify distinct groups of patients who might benefit from RIPC in the clinical setting and to reveal the effectiveness of cardioprotection delivered by plasma samples of these groups of patients. Methods RIPC (3 x 5 min arm ischemia, induced by an inflated blood pressure cuff) was performed on young and healthy volunteers and elderly patients with coronary heart disease with or without diabetes mellitus. Blood was taken before (Baseline) and 30 minutes after the intervention. The coronary system of murine hearts in a Langendorff heart model was perfused using dialysate from the human plasma obtained before and after RIPC. This was followed by 40 minutes of global ischemia. After 60 minutes of reperfusion left ventricular function was analysed. The infarct size was measured after 120 minutes reperfusion time using a TTC staining. Results Addition of dialysate of plasma obtained from healthy volunteers after RIPC to the coronary system of Langendorff perfused murine hearts significantly improved the recovery of left ventricular developed pressure (39±15.1 vs 26±8.5% of baseline levels, p=0.04) and reduced the infarct size (37.5±15.6 vs 21.2±11.4% of the ventricular volume, p=0.03) compared to baseline-dialysate treated controls. While plasma dialysate obtained from elderly patients with DM undergoing RIPC failed to show significant cardio protective effects of RIPC, murine hearts treated with plasma dialysate of elderly patients with coronary heart disease without diabetes after undergoing RIPC showed significant improvement of cardiac function (20±6.5 vs 24±7% of baseline levels, p=0.02) and infarct size (33.2±8.0 vs 11.1±2.5% of the ventricular volume, p=0.01). Conclusion The cardio-protective effect of RIPC on myocardial function and infarct size after I/R is influenced by diabetes but not by age or the presence of coronary heart disease. In consequence, RIPC might protect patients with coronary heart disease without DM but not diabetic patients from cardiac I/R injury. This important finding potentially explains why RIPC yielded promising results in various basic science experiments but failed to show cardio protective effects in clinical trials. Acknowledgement/Funding Forschungskommission of the Faculty of Medicine of the Heinrich-Heine-University Düsseldorf

scholarly journals Hydrogen-Rich Saline Protects against Ischemia/Reperfusion Injury in Grafts after Pancreas Transplantations by Reducing Oxidative Stress in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhu-Lin Luo ◽  
Long Cheng ◽  
Jian-Dong Ren ◽  
Chen Fang ◽  
Ke Xiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Proinflammatory Cytokines ◽  
Normal Saline ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Pancreatic Ischemia

Purpose.This study aimed to investigate the therapeutic potential of hydrogen-rich saline on pancreatic ischemia/reperfusion (I/R) injury in rats.Methods.Eighty heterotopic pancreas transplantations (HPT) were performed in syngenic rats. The receptors were randomized blindly into the following three groups: the HPT group and two groups that underwent transplantation and administration of hydrogen-rich saline (HS, >0.6 mM, 6 mL/kg) or normal saline (NS, 6 mL/kg) via the tail vein at the beginning of reperfusion (HPT + HS group, HPT + NS group). Samples from the pancreas and blood were taken at 12 hours after reperfusion. The protective effects of hydrogen-rich saline against I/R injury were evaluated by determining the changes in histopathology and measuring serological parameters, oxidative stress-associated molecules, and proinflammatory cytokines.Results.Administration of hydrogen-rich saline produced notable protection against pancreatic I/R injury in rats. Histopathological improvements and recovery of impaired pancreatic function were observed. In addition, TNF-α, IL-1β, and IL-6 were reduced markedly in the HPT + HS group. Additionally, there were noticeable inhibitory effects on the pancreatic malondialdehyde level and considerable recruitment of SOD and GPx, which are antioxidants.Conclusion.Hydrogen-rich saline treatment significantly attenuated the severity of pancreatic I/R injury in rats, possibly by reducing oxidative stress and inflammation.

scholarly journals Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaella Mastrocola ◽  
Claudia Penna ◽  
Francesca Tullio ◽  
Saveria Femminò ◽  
Debora Nigro ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Protective Effects ◽  
Risk Pathway ◽  
Lactate Dehydrogenase Release ◽  
Pyrin Domain

Although the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome has been recently detected in the heart, its role in cardiac ischemia/reperfusion (IR) is still controversial. Here, we investigate whether a pharmacological modulation of NLRP3 inflammasome exerted protective effects in an ex vivo model of IR injury. Isolated hearts from male Wistar rats (5-6 months old) underwent ischemia (30 min) followed by reperfusion (20 or 60 min) with and without pretreatment with the recently synthetized NLRP3 inflammasome inhibitor INF4E (50 μM, 20 min before ischemia). INF4E exerted protection against myocardial IR, shown by a significant reduction in infarct size and lactate dehydrogenase release and improvement in postischemic left ventricular pressure. The formation of the NLRP3 inflammasome complex was induced by myocardial IR and attenuated by INF4E in a time-dependent way. Interestingly, the hearts of the INF4E-pretreated animals displayed a marked improvement of the protective RISK pathway and this effect was associated increase in expression of markers of mitochondrial oxidative phosphorylation. Our results demonstrate for the first time that INF4E protected against the IR-induced myocardial injury and dysfunction, by a mechanism that involves inhibition of the NLRP3 inflammasome, resulting in the activation of the prosurvival RISK pathway and improvement in mitochondrial function.

scholarly journals Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Qiu-Yan Zhang ◽  
Zhi-Jun Wang ◽  
De-Miao Sun ◽  
Ying Wang ◽  
Peng Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tight Junction ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Brain Diseases ◽  
Therapeutic Effects ◽  
Protective Effects

Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted fromHerba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R), consistent results were obtained with decreased reactive oxygen species (ROS) production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC-) 4 which could inhibit NADPH oxidase- (NOX-) 4 and matrix metalloproteinase- (MMP-) 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO-) 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

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