Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Matsuki, Akira; Igawa, Akihiko; Nozawa, Takashi; Nakadate, Teruo; Igarashi, Norio; Nonomura, Makoto; Inoue, Hiroshi

doi:10.1253/circj.70.1643

Cited by 28 publications

(23 citation statements)

References 43 publications

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“…heart, brain, kidney or liver (108,109). Recent studies suggested a potential implication of HMGB1 signalling in IRI (110).…”

Section: Hmgb1 In Ischemic and Reperfusion Injurymentioning

confidence: 99%

HMGB1 and its physiological and pathological roles

Naglova¹,

Bucová²

2012

BLL

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HMGB1 has been formerly known for its intracellular function -as the intranuclear non-histone DNA binding protein, which contributes to stabilization of nucleosomes, mediation of DNA bending and is regarded to have an essential position in DNA repair. Lately, its participation in innate and specifi c immune responses has been revealed. Passively released from necrotic cells or actively produced by various cell types it acts as an alarmin and is responsible for production of pro-infl ammaory cytokines. HMGB1 is able to interact with RAGE and TLRs, receptors that belong into family of pattern recognition receptors and are involved in activation of pathways leading to production of pro-infl ammatory cytokines. Its key role has been revealed in mediation of sepsis and as it is released later than other pro-infl ammatory cytokines it became known as a "late mediator of sepsis". HMGB1 also contributes to the development of atherosclerosis and autoimmune diseases, e.g. its association with immunopathogenesis of SLE and RA has been suggested. Beside its negative function, HMGB1 protein seems to be able to attract stem cells to the area of infl ammation and thus promotes regeneration processes. This paradoxical function of HMGB1 protein has also been revealed in growth and spread of many types of tumours. HMGB1 represents a potential target in therapy of various disorders related to infl ammation (Fig. 2, Ref. 137). Full Text in PDF www.elis.sk.

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“…heart, brain, kidney or liver (108,109). Recent studies suggested a potential implication of HMGB1 signalling in IRI (110).…”

Section: Hmgb1 In Ischemic and Reperfusion Injurymentioning

confidence: 99%

HMGB1 and its physiological and pathological roles

Naglova¹,

Bucová²

2012

BLL

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“…Statins may improve endothelial function by decreasing expression of endothelial adhesion molecules, increasing nitric oxide bioavailability, and attenuating the production of reactive oxygen species. 2,21,22 In addition, statins are thought to stabilize plaque by decreasing lipid oxidation, inflammation, matrix metalloproteinase-2, and cell death and by increasing the content of tissue inhibitor of metalloproteinase-1 and collagen; these effects might reduce distal embolization. 23 Furthermore, statins have been shown to open mitochondrial adenosine triphosphate-sensitive potassium channels, suggesting pharmacological ischemic preconditioning effects.…”

Section: Statins and Myocardial Damagementioning

confidence: 99%

Effects of Pretreatment With Statins on Infarct Size in Patients With Acute Myocardial Infarction Who Receive Fibrinolytic Therapy

Kiyokuni

Kosuge

Ebina

et al. 2009

Circ J

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Circ J 2009; 73: 330 -335 tatins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used clinically to decrease serum cholesterol levels. 1 Recent studies have focused on the pleiotropic effects of statins, which are independent of their lipid-lowering effects, such as stimulation of fibrinolysis by altering the levels and activities of tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1. 2,3 Statins also reduce hemostasis by inhibiting platelet activation and the procoagulation cascade, and by augmenting the anticoagulation cascade. 4 Thus, statins appear to effectively enhance the fibrinolytic activity of t-PA. An experimental study in animals has shown that combination treatment with a statin and t-PA after stroke increases cerebral blood flow and reduces infarct volume as compared with fibrinolytic treatment alone; 5 however, data in humans are lacking. Prompt reperfusion of the occluded artery is crucial to limiting the size of an infarct. The present study was designed to test the hypothesis that statin treatment before the onset of acute myocardial infarction (AMI) contributes to prompt coronary artery reperfusion and smaller infarct size in patients with AMI who receive fibrinolytic therapy. We examined the relationship between statin pretreatment and the rate of coronary artery reperfusion assessed according to the Thrombolysis In Myocardial Infarction (TIMI) 6 flow grade and infarct size in patients with AMI who were given fibrinolytic therapy. The degree of myocardial damage before and after reperfusion therapy was also assessed on the basis of electrocardiographic (ECG) findings. Methods Study PopulationWe enrolled 310 consecutive patients with ST-segment elevation AMI (mean age 60±11 years; 268 men, 42 women) who fulfilled the following criteria: (1) no history of myocardial infarction; (2) admission to Yokohama City University Medical Center within 12 h of symptom onset; (3) absence of conditions precluding the evaluation of ST-segment changes on ECG (left or right bundle-branch block, ventricular pacing); and (4) received fibrinolytic therapy. The diagnosis of AMI was based on typical chest pain lasting at least 30 min, ST-segment elevation of at least 1 mm in 2 contiguous leads, and a subsequent increase in the serum creatine kinase (CK) level to more than twice the upper limit of normal. Cardiac symptoms occurring within 48 h before the onset of AMI were defined as preinfarction angina. 7 In Yokohama City University Medical Center, in principle, patients without any contraindications for fibrinolysis were given 200 mg oral aspirin, 50 IU/kg intravenous heparin, and (Received June 11, 2008; revised

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“…Numerous mechanisms of I/R injury have been revealed including the involvement of nitric oxide, generation of oxygen-derived free radicals, complement activation and infiltration of neutrophils into the ischemic area [5] . Most of these mechanisms will ultimately produce irreversible apoptotic injury to the myocardial tissues.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway

Zhai

Zhang

Zhang³

et al. 2012

Acta Pharmacol Sin

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Aim: Glycyrrhizin (GL) has been found to inhibit extracellular HMGB1 cytokine's activity, and protect spinal cord, liver and brain against I/R-induced injury in experimental animals. The purpose of this study was to investigate the protective effect of GL in rat myocardial I/R-induced injury and to elucidate the underlying mechanisms. Methods: Male adult Sprague-Dawley rats underwent a 30-min left coronary artery occlusion followed by a 24-h reperfusion. The rats were treated with glycyrrhizin or glycyrrhizin plus recombinant HMGB1 after 30 min of ischemia and before reperfusion. Serum HMGB1, TNF-α and IL-6 levels, and hemodynamic parameters were measured at the onset and different time points of reperfusion. At the end of the experiment, the heart was excised, and the infarct size and histological changes were examined. The levels of Bcl2, Bax and cytochrome c, as well as phospho-ERK1/2, phospho-JNK and phospho-P38 in the heart tissue were evaluated using Western blot analysis, and myocardial caspase-3 activity was measured colorimetrically using BD pharmingen caspase 3 assay kit. Results: Intravenous administration of GL (10 mg/kg) significantly reduced the infarct size, but did not change the hemodynamic parameters at different time points during reperfusion. GL significantly decreased the levels of serum HMGB1, TNF-α and IL-6. GL changed the distribution of Bax and cytochrome c expression between the mitochondrial and cytosolic fractions in the heart tissue, resulting in inhibition of myocardial apoptosis. Moreover, expression of phospho-JNK, but not ERK1/2 and P38 was decreased by GL in the heart tissue. All of the effects produced by GL treatment were reversed by co-administration with the recombinant HMGB1 (100 µg). Intravenous administration of SP600125, a selective phospho-JNK inhibitor (0.5 mg/kg), attenuated HMGB1-dependent Bax translocation and the subsequent apoptosis.Conclusion: These results demonstrate that GL alleviates rat myocardial I/R-induced injury via directly inhibiting extracellular HMGB1 cytokine activity and blocking the phospho-JNK/Bax pathway.

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Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Cited by 28 publications

References 43 publications

HMGB1 and its physiological and pathological roles

HMGB1 and its physiological and pathological roles

Effects of Pretreatment With Statins on Infarct Size in Patients With Acute Myocardial Infarction Who Receive Fibrinolytic Therapy

Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway

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