Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of oxidative contributions to aging has reached sufficient maturity to support the development of interventional strategies designed to forestall or reverse protein cross-linking, oxidation of DNA and lipids, and mitochondrial senescence associated with chronic pathology and aging. Catalytic antioxidants, including combined superoxide dismutase (SOD) and catalase mimics, extend the lifespan of oxidatively compromised animals such as Mn-SOD knockout mice, and will be entering the clinic for radiation-induced dermatitis. Substituted phenacylthiozolium compounds that slow the formation and break extant protein cross-linkages formed via Maillard reactions, restoring vascular compliance in aged animals, and are showing efficacy in clinical trials. Non-feminizing estrogen analogs (eg, 17- alpha estradiol) block cytotoxicity in a host of oxidative stress models and moderate neuronal loss in MCAO stroke models. Efficacy of the polycyclic phenols is synergistically amplified by glutathione supplementation, suggesting that the two function as a redox couple analogous to vitamin E and ascorbate. Finally, discovery of novel small molecules designed to stabilize mitochondrial function during Ca(2+)-induced oxidative stress, such as that occurring during stroke or myocardial ischemia reperfusion, will be accelerated by a proprietary fluorescence resonance energy transfer assay developed at MitoKor. Maintaining mitochondrial function under these circumstances will improve cellular bioenergetic and oxidative status, and hence moderate secondary necrosis and apoptosis.
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PMID:Oxidative Stress and Aging - Second International Conference. Technologies for assessment and intervention strategies. 2-5 April 2001, Maui, USA. 1599 30

Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ETA-ETB endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175-250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10% formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p < 0.05) in the myocardial malondialdehyde levels and a decrease (p < 0.01) in the myocardial reduced glutathione content. These changes were associated with significant decreases in the myocardial activity of antioxidant enzymes superoxide dismutase (p < 0.05) and catalase (p < 0.01) and severe tissue damage in the jeopardized myocardium in the CON group as compared with the non-myocardial ischemia-reperfusion (NMI-R) SHAM group. Bosentan exerted marked tissue protective effect as assessed by histologic evaluation of the myocardium. The drug significantly (p < 0.05) attenuated myocardial oxidative stress and restored the cellular antioxidant defense mechanisms as compared with the saline-treated controls subjected to the MI-R protocol. Furthermore, bosentan also exerted a marked effect on peripheral hemodynamics and heart rate during the reperfusion phase (data reported elsewhere). These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.
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PMID:Bosentan, the mixed ETA-ETB endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion. 1633 85

Oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of ischemic heart disease patients. Recently, it was found that endurance training elevates protective heat shock proteins (HSPs) and antioxidant enzymes in skeletal muscle in healthy subjects and antioxidant enzymes in heart failure patients. However, it is unknown whether coronary ischemia and mild infarct without heart failure contributes to impairment of stress proteins and whether exercise training reverses those effects. We tested the hypothesis that exercise training would reverse alterations in muscle TNF-alpha, oxidative stress, HSP70, SOD (Mn-SOD, Cu,Zn-SOD), glutathione peroxidase (GPX), and catalase (CAT) due to chronic coronary occlusion of the left circumflex (CCO). Yucatan swine were divided into three groups (n = 6 each): sedentary with CCO (SCO); 12 wk of treadmill exercise training following CCO (ECO); and sham surgery controls (sham). Forelimb muscle mass-to-body mass ratio decreased by 27% with SCO but recovered with ECO. Exercise training reduced muscle TNF-alpha and oxidative stress (4-hydroxynonenal adducts) caused by CCO. HSP70 levels decreased with CCO (-45%), but were higher with exercise training (+348%). Mn-SOD activity, Mn-SOD protein expression, and Cu,Zn-SOD activity levels were higher in ECO than SCO by 72, 82, and 112%, respectively. GPX activity was 177% greater in ECO than in SCO. CAT trended higher (P = 0.059) in ECO compared with SCO. These data indicate that exercise training following onset of coronary artery occlusion results in recovery of critical stress proteins and reduces oxidative stress.
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PMID:Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion. 1687 55

The aim of the study was to examine changes in the system lipid peroxidation-antioxidant defense (LPO-AOD) in patients with ischemic heart disease (IHD) exercising on the bicycle in free load regime. A course of standard medication in IHD patients reduced the level of lipid peroxidation by 15.1% (p < 0.05), on the average, malonic dialdehyde (MDA)--by 21.4% (p < 0.05), but at the end of the treatment these parameters did not reach those of healthy subjects and remained higher than they had. The addition of bicycle exercise in the treatment reduced LPO to the level of healthy subjects. AOD also changed in trained IHD patients: catalase activity rose in the trained patients by 22.6% (p < 0.001), on the average, that of superoxide dismutase--by 19.0% (p < 0.05). Total antioxidant activity of erythrocytes in trained patients rose by 24.0% (p < 0.01), total antioxidant activity of plasma increased by 43.3%. Thus, free bicycle exercise raises antiradical potential of blood in IHD patients. The effect of the exercise was the highest on the enzymes of AOD system.
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PMID:[Correction of free radical processes in patients with ischemic heart disease using bicycle exercise with free choice of load]. 1720 Dec 15

Catalase is a central antioxidant enzyme constituting the primary defense against oxidative stress. In this study, we investigated whether the functional -262C/T polymorphism in the promoter of catalase gene is associated with the presence of diabetic retinopathy (DR), diabetic nephropathy (DN) and ischemic heart disease (IHD) in 520 Caucasian-Brazilians with type 2 diabetes. The -262C/T polymorphism was also examined in 100 Caucasian blood donors. Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and laboratory tests. Genotype analysis was performed using the polymerase chain reaction followed by digestion with restriction enzyme. The genotype and allele frequencies of the -262C/T polymorphism in patients with type 2 diabetes were very similar to those of blood donors (T allele frequency=0.20 and 0.18, respectively). Likewise, there were no differences in either genotype or allele frequencies between type 2 diabetic patients with or without DR, DN or IHD. Thus, our results do not support the hypothesis that the -262C/T polymorphism is related to the development of DR, DN or IHD in patients with type 2 diabetes. Further studies are necessary to elucidate the role of catalase gene polymorphisms in the pathogenesis of diabetic complications.
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PMID:The catalase -262C/T promoter polymorphism and diabetic complications in Caucasians with type 2 diabetes. 1726 7

Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from ischemia-reperfusion injury. This review summarises the role of myocardial antioxidant enzymes in ischemia-reperfusion injury, particularly the glutathione peroxidase (GPX) and the thioredoxin reductase (TxnRed) systems. GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium. Moreover, various studies suggest that the supply of selenium as a cofactor also regulates gene expression of these selenoproteins. As such, dietary selenium supplementation may provide a safe and convenient method for increasing antioxidant protection in aged individuals, particularly those at risk of ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial hypoxia.
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PMID:Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. 1758 62

Recently, we have reported that purified Salvia miltiorrhiza extract (PSME) could prevent myocardial infarction in vivo and myocardial ischemia/reperfusion injury in isolated rat hearts (ex vivo). The aim of this project is to determine whether PSME exerts any cardioprotective effects in vitro. The vascular smooth muscle cell line was used and the effects of the drugs were determined after inducing hypoxia. Gene expression levels of the pro-apoptotic genes Asp53, Bax, and Fas were significantly down-regulated by 0.78-, 0.82-, and 0.87-fold, respectively, and Bcl-2 was up-regulated by 0.82-fold in the PSME-treated groups as compared to the hypoxic group (P<0.05). Significant reduction in immunoreactivity of the protein products of these genes as well as least nuclear green fluorescence observed in TUNEL staining indicate the therapeutic potential of this drug. Furthermore, cardiac antioxidant enzymes assay confirmed this deduction as PSME had slight preserving effects on superoxide dismutase and catalase (0.25 +/- 0.01 vs 0.488 +/- 0.02 units/mg protein and 0.026 +/- 0.012 vs 0.076 +/- 0.01 mumol per min per mg protein, respectively; each P<0.05). No significant results were obtained with glutathione S-transferase and GSH peroxidase antioxidant tests. Our results demonstrated that PSME exerts antioxidant effects in vitro, indicating the therapeutic potential of this drug.
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PMID:Effects of purified Salvia miltiorrhiza extract on cardiac vascular smooth muscle hypoxic cells. 1765 8

The observed 26 subjects with chronic heart failure (CHF) resulted from ischemic heart disease and it was found that the state of correlation interrelation between indices of lipid peroxidation of the antioxidant system and hemocoagulation is determined by the severity of decompensation. Patients with stage I CHF were seen to have a close direct interrelation between the content of primary and secondary by-products of lipid peroxidation and prothrombin time (PT). Patients with stage IIA CHF were observed with a close negative interrelation between the level of common lipids and recalcification time; vitamin A concentration and fibrinogen F. Patients with stage II CHF had direct interrelation between the level of common lipids, vitamins E, A and prothrombin index and inversely proportional to prothrombin time at the same time the catalase activity of the patients inversely correlated with fibrinogen F.
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PMID:[Interrelation between lipid peroxidation and indices of hemocoagulation in patients with chronic heart failure resulted from ischemic heart disease]. 1768 13

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)-(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.
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PMID:Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats. 1797 64

121 patients aged 35 to 85 years with ischemic heart disease (IHD) were observed. All the patients formed two age groups, mature and elderly. The 1st group consisted of women aged 35 to 55 years and men aged 35 to 60 years, the 2nd group of women aged 55+ years and men aged 60+ years. The group of control consisted of 47 patients aged 18 to 56 years without authentically verified IHD. 11 (9.1%) patients died of cardiovascular reasons within one year from the moment of hospitalisation. All of them (middle age 71.4 +/- 7.4 years) were the patients of elderly age grouP. The regression analysis showed that among various parameters (increase level of protein in urine, urea, creatinine, IL-6 and von Willebrand factor in blood, heart contraction rate), the growth of level of myeloperoxidase accompanied by activity reduction of glutathione reductase in neutrophils has also been connected with the increase of lethal outcome risk. Besides in elderly patients unlike patients of mature age in the beginning of hospitalisation a decrease in antioxidative protection activity (catalase) in neutrophils accompanied by an increase in IL-6 contents in blood not depended on presence diabetes mellitus type II and not connected with systolic dysfunction of heart left ventricle was found. It is possible to believe, that oppression antioxidative protection of neutrophils coming in process of ageing of an organism promotes in the conditions of stress uncontrollable manufacture reactive forms of oxygen damaging endothelium and breaking hemostasis, which results in death.
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PMID:[Age changes redox regulation metabolism and antioxidative protection of neutrophils in patients with ischemic heart disease]. 1943 75


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