Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Autophagy Is Involved in the Cardioprotection Effect of Remote Limb Ischemic Postconditioning on Myocardial Ischemia/Reperfusion Injury in Normal Mice, but Not Diabetic Mice  [PDF]
Zhihua Han, Jiatian Cao, Dongqiang Song, Lei Tian, Kan Chen, Yue Wang, Lin Gao, Zhaofang Yin, Yuqi Fan, Changqian Wang
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086838
Abstract: Background Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Methodology and Results Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p<0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p<0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. Conclusions The current study suggested that RIPostC exerts cardioprotection effect on IR in normal mice, but not DM mice, and this difference is via, at least in part, the up-regulation of autophagy.
Sca-1+ Cardiac Stem Cells Mediate Acute Cardioprotection via Paracrine Factor SDF-1 following Myocardial Ischemia/Reperfusion  [PDF]
Chunyan Huang, Hongmei Gu, Qing Yu, Mariuxi C. Manukyan, Jeffrey A. Poynter, Meijing Wang
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029246
Abstract: Background Cardiac stem cells (CSCs) promote myocardial recovery following ischemia through their regenerative properties. However, little is known regarding the implication of paracrine action by CSCs in the setting of myocardial ischemia/reperfusion (I/R) injury although it is well documented that non-cardiac stem cells mediate cardioprotection via the production of paracrine protective factors. Here, we studied whether CSCs could initiate acute protection following global myocardial I/R via paracrine effect and what component from CSCs is critical to this protection. Methodology/Principal Findings A murine model of global myocardial I/R was utilized to investigate paracrine effect of Sca-1+ CSCs on cardiac function. Intracoronary delivery of CSCs or CSC conditioned medium (CSC CM) prior to ischemia significantly improved myocardial function following I/R. siRNA targeting of VEGF in CSCs did not affect CSC-preserved myocardial function in response to I/R injury. However, differentiation of CSCs to cardiomyocytes (DCSCs) abolished this protection. Through direct comparison of the protein expression profiles of CSCs and DCSCs, SDF-1 was identified as one of the dominant paracrine factors secreted by CSCs. Blockade of the SDF-1 receptor by AMD3100 or downregulated SDF-1 expression in CSCs by specific SDF-1 siRNA dramatically impaired CSC-induced improvement in cardiac function and increased myocardial damage following I/R. Of note, CSC treatment increased myocardial STAT3 activation after I/R, whereas downregulation of SDF-1 action by blockade of the SDF-1 receptor or SDF-1 siRNA transfection abolished CSC-induced STAT3 activation. In addition, inhibition of STAT3 activation attenuated CSC-mediated cardioprotection following I/R. Finally, post-ischemic infusion of CSC CM was shown to significantly protect I/R-caused myocardial dysfunction. Conclusions/Significance This study suggests that CSCs acutely improve post-ischemic myocardial function through paracrine factor SDF-1 and up-regulated myocardial STAT3 activation.
ZFP580, a Novel Zinc-Finger Transcription Factor, Is Involved in Cardioprotection of Intermittent High-Altitude Hypoxia against Myocardial Ischemia-Reperfusion Injury  [PDF]
Xiang-yan Meng, Hai-long Yu, Wen-cheng Zhang, Tian-hui Wang, Xia Mai, Hong-tao Liu, Rui-cheng Xu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094635
Abstract: Background ZFP580 is a novel C2H2 type zinc-finger transcription factor recently identified by our laboratory. We previously showed that ZFP580 may be involved in cell survival and growth. The aim of this study was to elucidate whether ZFP580 is involved in the cardioprotective effects of intermittent high-altitude (IHA) hypoxia against myocardial ischemia-reperfusion (I/R) injury. Methods and Results After rats were subjected to myocardial ischemia for 30 min followed by reperfusion, ZFP580 expression in the left ventricle was measured. ZFP580 protein expression was found to be up-regulated within 1 h and decreased at 2 h after reperfusion. Comparing normoxic and IHA hypoxia-adapted rats (5000 m, 6 h day?1, 6 weeks) following I/R injury (30 min ischemia and 2 h reperfusion), we found that adaptation to IHA hypoxia attenuated infarct size and plasma leakage of lactate dehydrogenase and creatine kinase-MB. In addition, ZFP580 expression in the myocardium was up-regulated by IHA hypoxia. Consistent with this result, ZFP580 expression was found to be significantly increased in cultured H9c2 myocardial cells in the hypoxic preconditioning group compared with those in the control group following simulated I/R injury (3 h simulated ischemic hypoxia and 2 h reoxygenation). To determine the role of ZFP580 in apoptosis, lentivirus-mediated gene transfection was performed in H9c2 cells 72 h prior to simulated I/R exposure. The results showed that ZFP580 overexpression significantly inhibited I/R-induced apoptosis and caspase-3 activation. H9c2 cells were pretreated with or without PD98059, an inhibitor of ERK1/2 phosphorylation, and Western blot results showed that PD98059 (10 μM) markedly suppressed I/R-induced up-regulation of ZFP580 expression. Conclusions Our findings demonstrate that the cardioprotective effect of IHA hypoxia against I/R injury is mediated via ZFP580, a downstream target of ERK1/2 signaling with anti-apoptotic roles in myocardial cells.
Rohilla Ankur,Singh Gurfateh,Khan M.U.,Khanam Razia
International Research Journal of Pharmacy , 2011,
Abstract: The present study has been designed to investigate the effect of Simvastatin, a 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, on ischemia-reperfusion (I/R)-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial injury was assessed by measuring myocardial infarct size alongwith release of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent. Additionally, the oxidative stress parameters were analyzed in the heart which was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. I/R was noted to produce myocardial injury, as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent. Moreover, oxidative stress was noted to be increased due to I/R injury as assessed in terms of decreased TBARS (thiobarbituric acid-reactive substance) and superoxide anion generation levels alongwith increase in reduced glutathione levels in the heart. Treatment with Simvatstain at different concenterations (3 μMol, 10 μMol and 30 μMol) afforded cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent. Moreover, the high degree of oxidative stress produced as a result of I/R injury was noted to be reduced by Simvastatin treatment. It may be concluded that reductions in myocardial infarct size and oxidative stress may be responsible for the observed cardioprotective potential of Simvastatin against I/R-induced myocardial injury.
Comparative Effects of Verapamil, Nicardipine, and Nitroglycerin on Myocardial Ischemia/Reperfusion Injury  [PDF]
Hitoshi Yui,Uno Imaizumi,Hisashi Beppu,Mitsuhiro Ito,Munetaka Furuya,Hirofumi Arisaka,Kazu-Ichi Yoshida
Anesthesiology Research and Practice , 2011, DOI: 10.1155/2011/521084
Abstract: The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have (1) infarct size-limiting effects and (2) antiarrhythmic effects in in vivo rabbit hearts during ischemia/reperfusion. Rabbits received regional ischemia by 30?min of left anterior descending coronary artery occlusion followed by 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a verapamil group, a nicardipine group, and a nitroglycerin group. A continuous infusion of verapamil, nicardipine, or nitroglycerin was initiated 5?min prior to ischemia. Infarct size/area at risk decreased in verapamil, and nitroglycerin. The incidence of ischemia-induced arrhythmia decreased in nicardipine, verapamil and nitroglycerin. The incidence of reperfusion-induced arrhythmias decreased in verapamil and nitroglycerin. From the present experimental results, verapamil and nitroglycerin rather than nicardipine did afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model. 1. Introduction Myocardial ischemia/reperfusion injury and its prevention have become the focus of considerable attention. It was reported that intracellular calcium overload is a recognized common pathway that can explain ischemia/reperfusion injury [1]. Several studies have shown that -type calcium antagonists have beneficial effects on the ischemic myocardium by inhibiting transmembrane calcium influx in cardiac and vascular smooth muscle [2, 3]. On the other hand, previous experimental studies have investigated effects of nitric oxide (NO) donors to reduce myocardial ischemia/reperfusion injury [4, 5]. This cardioprotection is due to the mechanism that nitroglycerin is converted in vascular smooth muscle cells to NO and relaxes vascular muscle of the large veins and coronary arteries. As a result, nitroglycerin can reduce preload and also provide an increased blood flow to the heart. It is clear that calcium antagonists and NO donors have cardioprotective effects. However, there is no study examining the intensity of myocardial protection of these drugs as indexes of infarct size and arrhythmias. The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have infarct size-limiting effects and antiarrhythmic effects in in vivo rabbit hearts during ischemia/reperfusion. 2. Materials and Methods The present study was performed in accordance with the Guidelines of Animal Care and Use Committee of Kanagawa Dental College. 2.1.
Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury  [PDF]
Christine Herzog,Martina Schmitz,Bodo Levkau,Ilka Herrgott,Jan Mersmann,Jan Larmann,Kai Johanning,Michael Winterhalter,Jerold Chun,Frank Ulrich Müller,Frank Echtermeyer,Reinhard Hildebrand,Gregor Theilmeier
Mediators of Inflammation , 2010, DOI: 10.1155/2010/425191
Abstract: HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor. 1. Introduction High-density lipoproteins (HDL) exert beneficial effects on cardiovascular pathologies not only due to their effects on reverse cholesterol transport, but in addition through pleiotropic effects on vessel wall biology [1]. In addition to its effects on vessel wall pathology, HDL has been shown to protect from myocardial injury and necrosis during reperfusion after ischemia [2]. Adhesion of leukocytes to the vascular endothelium and subsequent transmigration are a characteristic feature of inflammation. Reduced recruitment of leukocytes during reperfusion after ischemic insult has been shown to be beneficial in numerous experimental settings [3, 4]. Likewise, apoptotic cell death is a mainstay of tissue damage secondary to reperfusion injury after transient ischemia [5]. Antiapoptotic effects have been demonstrated to reduce reperfusion-induced tissue damage [6]. However, there is an ongoing debate as to the causal role of apoptosis in infarct enlargement during reperfusion injury. We have recently demonstrated that high-density lipoproteins (HDL) protect from myocardial damage during reperfusion after ischemia due to the anti-inflammatory and antiapoptotic effects of its sphingophospholipid (SPL) component, sphingosine-1-phosphate [7]. Like S1P, sphingosylphosphorylcholine (SPC) represents a major SPL species circulating with HDL. Several groups have shown that SPC, similar to
Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro
Huaying Fan,Liu Yang,Fenghua Fu,Hui Xu,Qinggang Meng,Haibo Zhu,Lirong Teng,Mingyan Yang,Leiming Zhang,Ziliang Zhang,Ke Liu
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/508938
Abstract: Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application.
Impairment of Endothelial-Myocardial Interaction Increases the Susceptibility of Cardiomyocytes to Ischemia/Reperfusion Injury  [PDF]
Thorsten M. Leucker, Zhi-Dong Ge, Jesse Procknow, Yanan Liu, Yang Shi, Martin Bienengraeber, David C. Warltier, Judy R. Kersten
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070088
Abstract: Endothelial-myocardial interactions may be critically important for ischemia/reperfusion injury. Tetrahydrobiopterin (BH4) is a required cofactor for nitric oxide (NO) production by endothelial NO synthase (eNOS). Hyperglycemia (HG) leads to significant increases in oxidative stress, oxidizing BH4 to enzymatically incompetent dihydrobiopterin. How alterations in endothelial BH4 content impact myocardial ischemia/reperfusion injury remains elusive. The aim of this study was to examine the effect of endothelial-myocardial interaction on ischemia/reperfusion injury, with an emphasis on the role of endothelial BH4 content. Langendorff-perfused mouse hearts were treated by triton X-100 to produce endothelial dysfunction and subsequently subjected to 30 min of ischemia followed by 2 h of reperfusion. The recovery of left ventricular systolic and diastolic function during reperfusion was impaired in triton X-100 treated hearts compared with vehicle-treated hearts. Cardiomyocytes (CMs) were co-cultured with endothelial cells (ECs) and subsequently subjected to 2 h of hypoxia followed by 2 h of reoxygenation. Addition of ECs to CMs at a ratio of 1:3 significantly increased NO production and decreased lactate dehydrogenase activity compared with CMs alone. This EC-derived protection was abolished by HG. The addition of 100 μM sepiapterin (a BH4 precursor) or overexpression of GTP cyclohydrolase 1 (the rate-limiting enzyme for BH4 biosynthesis) in ECs by gene trasfer enhanced endothelial BH4 levels, the ratio of eNOS dimer/monomer, eNOS phosphorylation, and NO production and decreased lactate dehydrogenase activity in the presence of HG. These results demonstrate that increased BH4 content in ECs by either pharmacological or genetic approaches reduces myocardial damage during hypoxia/reoxygenation in the presence of HG. Maintaining sufficient endothelial BH4 is crucial for cardioprotection against hypoxia/reoxygenation injury.
Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats
Rui Xia,Bo Zhao,Yang Wu,Jia-Bao Hou,Li Zhang,Jin-Jin Xu,Zhong-Yuan Xia
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/767930
Abstract: Diabetes mellitus is associated with decreased NO bioavailability in the myocardium. Ginsenoside Rb1 has been shown to confer cardioprotection against ischemia reperfusion injury. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing eNOS expression in the myocardium. The myocardial I/R injury were induced by occluding the left anterior descending artery for 30 min followed by 120 min reperfusion. An eNOS inhibitor L-NAME or Rb1 were respectively administered 25 min or 10 min before inducing ischemia. Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group. Ginsenoside Rb1 induced myocardial protection was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH (<0.05). Moreover, the myocardial oxidative stress and tissue histological damage was attenuated by Ginsenoside Rb1 (<0.05). L-NAME abolished the protective effects of Ginsenoside Rb1. It is concluded that Ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress.
Protection against Myocardial Ischemia-Reperfusion Injury at Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats Is Associated with Altered Glucose Oxidation  [PDF]
Jonas Agerlund Povlsen, Bo L?fgren, Christian Dalgas, Rune Isak Dupont Birkler, Mogens Johannsen, Nicolaj Brejnholt St?ttrup, Hans Erik B?tker
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064093
Abstract: Background Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR) injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM). We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. Methods Isolated perfused hearts from 6 (prediabetic), 12 (onset of T2DM) and 24 (late T2DM) weeks old male Zucker diabetic fatty rats (ZDF) and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates), myocardial microdialysis (metabolomics) and tissue glycogen measurements. Results T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. Conclusions The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes.
Page 1 /100
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.