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myeloperoxidase and High-Sensitivity C-Reactive Protein for Predicting Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease

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International Journal of Clinical Medicine 2015年第4期6卷 262-270页

作者： Chenggui Liu Linong Chen Yinzhong Yang Cheng Huang Jun Luo Duanliang Peng Department of Clinical Laboratory Chengdu Women’s and Children’s Central Hospital Chongqing Medical University Chengdu China Department of Clinical Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital Chengdu China

Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.

关键词： myeloperoxidase High Sensitivity C-Reactive Protein Acute Coronary Syndrome Coronary Heart Disease Major Adverse Cardiovascular Events

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Functional annotation and enrichment analysis of differentially expressed serum proteins in patients with type 2 diabetes after dapagliflozin

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World Journal of Diabetes 2022年第3期13卷 224-239页

作者： Yan-Xue Zhao Sarul Borjigin Zhao-Li Yan Basic Building Laboratory The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010000Inner MongoliaChina Department of Endocrinology The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010000Inner MongoliaChina

BACKGROUND Only 50% of patients with type 2 diabetes mellitus(T2DM) can control their blood glucose levels. Dapagliflozin is a selective inhibitor of sodium-glucose cotransporter 2(SGLT-2) that improves the insulin sensitivity of the liver and peripheral tissues. Many studies confirmed that SGLT2 inhibitors reduce blood glucose and have multiple beneficial effects such as weight loss, lipid regulation, and kidney protection. Nevertheless, the mechanisms of the renal and cardiovascular protective effects of dapagliflozin from the perspective of differentially expressed proteins in the serum of T2DM patients have not been intensively explored so far.AIM To identify differentially expressed proteins associated with dapagliflozin treatment in patients with T2DM.METHODS Twenty T2DM patients [hemoglobin A1c(HbA1c) 7.0%-10.0%] were enrolled at The Affiliated Hospital of Inner Mongolia Medical University between January 1, 2017 and December 1, 2018. They received dapagliflozin(10 mg/d) for 3 mo, and the HbA1c myeloperoxidase(MPO) and alpha Ⅱ B integrin(ITGA2B), and one upregulated protein, podocalyxin(PCX), were selected for enzyme li

关键词： Type 2 diabetes mellitus Dapagliflozin Non-standard quantitative proteomics myeloperoxidase Alpha II B integrin Podocalyxin

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Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation

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Acta Pharmaceutica Sinica B 2023年第1期13卷 390-409页

作者： Qiang Nie Chenwen Li Yu Wang Yi Hu Wendan Pu Qixiong Zhang Jiajun Cai Yongyao Lin Gang Li Chenping Wang Lanlan Li Yin Dou Jianxiang Zhang Department of Pharmaceutics College of PharmacyThird Military Medical University(Army Medical University)Chongqing 400038China Department of Radiology Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer HospitalChongqing 400030China State Key Lab of Trauma Burn and Combined InjuryInstitute of Combined InjuryThird Military Medical University(Army Medical University)Chongqing 400038China

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases.However,effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases.Herein we report a novel strategy for engineering inflammationaccumulation nanoparticles via phenolic functionalization.Different phenol-functionalized nanoparticles were first developed,which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment.Phenolic compound-decorated poly(lactide-co-glycolide)nanoparticles,in particular tyramine(Tyr)-coated nanoparticles,showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis,acute liver injury,and acute lung injury,mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species.By combining a cyclodextrin-derived bioactive material with Tyr decoration,a multifunctional nanotherapy(TTN)was further developed,which displayed enhanced cellular uptake,antiinflammatory activities,and inflammatory tissue accumulation,thereby affording amplified therapeutic effects in mice with colitis or acute liver injury.Moreover,TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration,leading to considerably potentiated in vivo efficacies.Preliminary studies also revealed good safety of orally delivered TTN.Consequently,Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

关键词： Inflammatory disease Reactive oxygen species myeloperoxidase Targeted therapy Nanoparticles Surface engineering Triggerable aggregation Nanotherapy

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Carbamylated lipoproteins in diabetes

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World Journal of Diabetes 2023年第3期14卷 159-169页

作者： Damien Denimal Department of Biochemistry University Hospital of DijonDijon 21079France INSERM LNC UMR1231 University of BurgundyDijon 21078France

Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

关键词： Carbamylation Lipoprotein Diabetes Low-density lipoprotein High-density lipoprotein myeloperoxidase

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Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns(With video)

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Burns & Trauma 2021年第1期9卷 240-254页

作者： Lu Liu Yiming Shao Yixuan Zhang Yunxi Yang Jiamin Huang Linbin Li Ran Sun Yuying Zhou Yicheng Su Bingwei Sun School of Medicine Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Burns and Plastic Surgery Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215002Jiangsu ProvinceChina

Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted inter

关键词： Severe burn Heparin binding protein myeloperoxidase Vascular leakage Glycocalyx

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Association between Plasma myeloperoxidase and Free 3-Nitrotyrosine Levels in Patients with Coronary Artery Disease

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International Journal of Clinical Medicine 2013年第3期4卷 158-164页

作者： Morteza Pourfarzam Ahmad Movahedian Nizal Sarrafzadegan Gholam Basati Saed Ziaaldin Samsamshariat Cardiovascular Research Center Isfahan Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran Department of Clinical Biochemistry Faculty of Medicine Ilam University of Medical Sciences Ilam Iran Pharmaceutical Sciences Research Centre Department of Clinical Biochemistry School of Pharmacy and Pharmaceutical Sciences Isfahan University of Medical Sciences Isfahan Iran Pharmaceutical Sciences Research Centre Department of Clinical Biochemistry School of Pharmacy and Pharmaceutical Sciences Isfahan University of Medical Sciences Isfahan Iran.

Objective: myeloperoxidase (MPO) is an inflammatory enzyme that is mainly released by activated neutrophils and monocytes. 3-nitrotyrosine (NT) is a stable inflammatory end product of MPO that is produced through nitrosylation of free and protein-bound tyrosines. Determination of the exact levels of free NT is technically a challenging matter. Also, there is limited information about the relationship between MPO and free NT levels and elevation of them in the plasma of patients with coronary artery disease (CAD). Therefore, we sought to determine the exact level of plasma free NT with a simple and exquisite technique in CAD patients. Methods: This study included 50 stable angina, 50 unstable angina patients, and 50 control subjects. Plasma MPO concentration was measured with an immunoassay method. Plasma free NT level was determined by a modified HPLC-fluorescence method. Lipid profile, high sensitivity C-reactive protein (hsCRP) and other clinical risk factors of patients were also assigned. Results: Plasma level of free NT was efficiently measured by the HPLC-fluorescence method. Plasma levels of MPO and NT were significantly higher in patients with stable and unstable CAD than in control subjects (P < 0.001). There was a significant correlation between the two substances in CAD patients (P < 0.001). Conclusions: We determined plasma free NT levels with a sensitive HPLC-fluorescence method with some modifications in a clinical scale. Plasma levels of MPO and NT were profoundly elevated in CAD patients. The significant relationships of the two substances and elevation of them may have useful clinical implication in patients with stable and unstable CAD.

关键词： myeloperoxidase 3-Nitrotyrosine Stable Unstable CAD

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Role of Lactic Acid Bacteria-myeloperoxidase Synergy in Establishing and Maintaining the Normal Flora in Man

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Food and Nutrition Sciences 2013年第11期4卷 67-72页

作者： Robert C. Allen Jackson T. Stephens Jr. Department of Pathology School of Medicine Creighton University Omaha USA ExOxEmis Inc. Little Rock USA

Lactic acid bacteria (LAB) are incapable of cytochrome synthesis and lack the heme electron transport mechanisms required for efficient oxygen-based metabolism. Consequently, LAB redox activity is flavoenzyme-based and metabolism is fermentative, producing lactic acid, and in many cases, hydrogen peroxide (H2O2). Despite this seeming metabolic limitation, LAB dominate in the normal flora of the mouth, vagina and lower gastrointestinal tract in man. myeloperoxidase (MPO) is produced by the neutrophil leukocytes and monocytes that provide the innate phagocyte defense against infecting pathogens. MPO is unique in its ability to catalyze the H2O2-dependent oxidation of chloride (Cl-) to hypochlorite (OCl-). In turn, this OCl- directly reacts with a second H2O2 to produce singlet molecular oxygen (), a metastable electronic excitation state of oxygen with a microsecond lifetime that restricts its combustive reactivity within a submicron radius of its point of generation. Each day a healthy human adult produces about a hundred billion neutrophils containing about 4 femtograms MPO per neutrophil. Inflammatory states and G-CSF treatment increase both neutrophil production and the quantity of MPO per neutrophil. After a short circulating lifetime, neutrophils leave the blood and migrate into body spaces including the mouth, vagina, urinary tract, and gastrointestinal tract. Greater than a hundred thousand neutrophils are lavaged from the mouths of healthy humans;the quantity lavaged is proportional to the blood neutrophil count. MPO selectively and avidly binds to most Gram-positive and all Gram-negative bacteria tested, but LAB do not show significant MPO binding. Neutrophils migrating to normal flora sites release MPO into the LAB-conditioned milieu containing adequate acidity and H2O2 to support extra-phagocyte MPO microbicidal action. In combination, LAB plus MPO exert a potent synergistic microbicidal action against high MPO-binding microbes. This LAB-MPO synergy provides a mechanism for the establishment and mainten

关键词： myeloperoxidase Lactic Acid Bacteria Hydrogen Peroxide Hypochlorite Singlet Oxygen Selective Binding Selective Microbicidal Action Normal Flora

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Introducing a Rapid and Safe Method for myeloperoxidase Staining

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Open Journal of Pathology 2015年第2期5卷 38-41页

作者： Fatemeh E. Mahjoub Fahimeh Firouzjaie Karder Issa Jahanzad Saghi Vaziri Ramezan Ali Sharifian Zahra Farahani Pathology Maternal Fetal and Neonatal Research Center Tehran University of Medical Sciences Tehran Iran Imam Khomeini Hospital Complex Central Laboratory and Cancer Institute Pathology Laboratory Tehran University of Medical Sciences Tehran Iran Valiasr Hospital Central Laboratory Tehran University of Medical Sciences Tehran Iran Imam Khomeini Hospital Complex Cancer Institute Tehran University of Medical Sciences Tehran Iran Hematology Oncology Imam Khomeini Hospital Complex Valiasr Hospital Tehran University of Medical Sciences Tehran Iran

Background: myeloperoxidase staining is used to differentiate leukemias since several decades. Despite implementation of flow cytometric, cytogenetic and molecular techniques for identification of leukemic blasts, histochemical stains such as myeloperoxidase stain are persistently used for better classification of leukemias. The myeloperoxidase staining is a time consuming and hazardous procedure. The present report describes a sensitive, rapid and easy method for assessment of peroxidase activity. Materials and Methods: Bone marrow aspiration slides were stained with Dako product: Code number: K3467 containing DAB chromogen (3,3-diaminobenzidine in chromogen solution) and substrate buffer (Imidasole-HCL buffer, PH 7.5 containing hydrogen peroxide and an anti microbial agent) in a rapid procedure taking only ten minutes time. The staining needs no material preparation steps. Neutrophils in the slide are taken as positive control or another normal smear was costained to be used as control. All cases were followed up with flow cytometry and cytogenetic studies. Result: The reaction product of this stain is brown and granular. Promyelocytes and myelocytes are the most strongly staining cells with positive (primary) granules. Lymphoblasts are negative. The result of classification of leukemias with this technique was in concordance with flow cytometric immunophenotyping. Discussion: Many practical techniques have been described using benzidine as an indicator for myeloperoxidase staining. Benzidine is a carcinogenic material and its usage is severely restricted in laboratory. Formerly we prepared requisite materials for myeloperoxidase staining by hazardous ways (boiling), but we decided to apply ready to use 3,3-diaminobenzidine (DAB), which is used in final step of immunohistochemistry stains. Conclusion: Use of 3,3-diaminobenzidine (DAB) is highly recommended for myeloperoxidase staining, while the result is extraordinary and fully compatible with flow cytometry and the method is safe and rapid.

关键词： myeloperoxidase Staining DAB 3 3-Diaminobenzidine Safe and Rapid Method

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Effect of honey on oxidation, chlorination and nitration by purified equine myeloperoxidase

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Journal of Coastal Life Medicine 2017年第9期5卷 398-402页

作者： Saad Aissat Hama Benbarek Thierry Franck Stephan Kohnen Didier Serteyn Moussa Ahmed Ange Mouithys-Mickalad Institute of Veterinary Sciences Ibn Khaldoun UniversityTiaret14000Algeria Pharmacognosy and Api-Phytotherapy Research Laboratory Mostaganem UniversityMostaganemAlgeria Faculty of Sciences of Nature and Life Mascara UniversityMascara29000Algeria Centre for Oxygen Research and Development(CORD)Institute of Chemistry B6aUniversity of LiègeSart Tilman4000Liège1Belgium Department of Clinical Sciences Large Animal SurgeryFaculty of Veterinary MedicineB41University of LiègeSart Tilman4000Liège1Belgium Celabor Centre de Services Scientifique et Technique aux EntreprisesZoning Industriel de Petit-RechainAvenue du Parc384650HerveBelgium

Objective: To evaluate the antioxidant effect of honey using two classical methods generally used, and for the first time to test the effect of honey on the oxidation, chlorination and nitration by purified equine myeloperoxidase (MPO). Methods: The antioxidant activity of three Algerian honey samples (nectar honey, mixed honey and honeydew honey) was evaluated by two classical methods, the ferric- reducing/antioxidant power (FRAP) assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity. Results: Honeydew honey had the highest reducing power and DPPH radical-scavenging activity, whereas nectar honey showed the lowest reducing power and DPPH radical-scavenging activity. All honey samples showed a significant inhibitory effect on the chlorination activity of equine MPO, but honeydew honey was the weakest inhibitor. The three samples were poorly inhibitor on the MPO oxidation and nitration activities, except for nectar honey that exerted an inhibitory effect at the highest tested concentration of 10%. These later results seem to contradict those obtained with DPPH and FRAP. Conclusions: The antioxidant capacity of honey is mainly due to the phenolic compounds and flavonoids it contained. It has been suggested that MPO might be involved in the antioxidant, not pro-oxidant, activity of phenolic compounds.

关键词： Honey myeloperoxidase Chlorination Oxidation Nitration

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Serum myeloperoxidase level is increased in heavy smokers

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Open Journal of Clinical Diagnostics 2013年第1期3卷 5-8页

作者： André B. Martins Valdecir F. Ximenes Luiz Marcos da Fonseca Departamento de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista-UNESP Araraquara Brasil Departamento de Química Faculdade de Ciências Universidade Estadual Paulista-UNESP Bauru Brasil

Raised myeloperoxidase (MPO) serum levels are associated with endothelial dysfunction and cigarette smoking is a risk factor for cardiovascular diseases. Since myocardial infarction is associated with leukocytosis and smokers present increased levels of neutrophils, here we hypothesized that the levels of serum MPO in smokers could be also raised. We carried out a study on sixty eight adult healthy volunteers. The control group consisted of thirty four non-smokers and the test group was thirty four heavy smokers. The hemogram, interleukin-8 (IL-8) and MPO serum levels were measured. Neutrophil, monocyte and lymphocyte counts were higher

关键词： Smokers Neutrophils IL-8 myeloperoxidase Hypochlorous Acid Atherosclerosis

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