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myeloperoxidase: a new target for the treatment of stroke?

Neural Regeneration Research 2022年第8期17卷 1711-1716页

作者： Yun-Chang Wang Yu-Bao Lu Xiao-Lan Huang Yong-Feng Lao Lu Zhang Jun Yang Mei Shi Hai-Long Ma Ya-Wen Pan Yi-Nian Zhang The Second Clinical Medical School Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Lanzhou University Second HospitalLanzhouGansu ProvinceChina Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina University of Chinese Academy of Sciences BeijingChina

myeloperoxidase is an important inflammatory factor in the myeloid system,primarily expressed in neutrophils and microglia.myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke,including damage to the blood-brain barrier and brain.As a specific inflammatory marker,myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke,and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis.Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke.The occurrence of stroke not only refers to the first occurrence but also includes recurrence.Therefore,myeloperoxidase is significant for the clinical evaluation and prognosis of stroke.This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis.This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

关键词： blood-brain barrier hemorrhagic stroke inflammation ischemic stroke microglia myeloperoxidase neutrophils secondary brain injury stroke

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Urinary myeloperoxidase to Creatinine Ratio as a New Marker for Diagnosis of Urinary Tract Infection

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Chinese Medical Sciences Journal 2018年第3期33卷 152-159页

作者： Mingjian Bai Jing Feng Guowei Liang Department of Clinical Laboratory Aerospace Central HospitalBeijing 100049China

Objective To determine whether urinary myeloperoxidase to creatinine ratio(MCR)can serve as a marker for diagnosis of urinary tract infection(UTI).Methods Patients suspected of UTI were consecutively enrolled and further divided into the culture positive and the sterile groups according to urine culture results.Subsequently,MCR,white blood cell(WBC)and bacteria in the urinary samples from patients were detected and compared between the two groups.Results Finally,253 patients were enrolled including 157 urine culture positive patients and 96 urine culture negative patients(sterile group).After logarithmic transformation in 2 as the base,the MCR,WBC,and bacteria were separately presented as log2 MCR,log2 WBC(quantitative),and log2 bacteria.The values of log2 MCR(8.6±2.5 vs.5.4±1.5,t=-12.453,P=0.001),log2 WBC(quantitative)(8.0±2.5 vs.5.2±1.8,t=-10.332,P=0.001),log2 bacteria(11.4±2.5 vs.8.2±2.8,t=-9.297,P=0.001)and WBC(semi-quantitative)[2(interquartile range 1,3)vs.1(interquartile range 0.5,1),Z=-7.580,P=0.001]showed significant difference between the urine culture positive group and the sterile group.Among the urine culture positive group,the values of log2 MCR of the gram positive and gram negative subgroups were 7.2±2.5 and 9.0±2.4(t=4.016,P=0.001),respectively.The correlation between log2 MCR and log2 WBC(quantitative),log2 bacteria,WBC(semi-quantitative)was 0.708(Pearson correlation,P=0.001),0.381(Pearson correlation,P=0.001),and 0.606(Spearman correlation,P=0.001),respectively.Conclusions MCR is positively correlated with WBC counts and could be served as a promising biomarker for diagnosis of UTI.MCR could be even used for initial inference of infectious bacteria types of UTI.

关键词： urine myeloperoxidase diagnosis urinary tract infection

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myeloperoxidase Aggravates Myocardial Vulnerability to Ischemia/Reperfusion Injury via Disruption of the Nitric Oxide-cGMP Pathway in Rats with Hypercholesterolemia

Myeloperoxidase Aggravates Myocardial Vulnerability to Ische...

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2019年中国生理学会心血管生理学术研讨会

作者： Ye Wu Huirong Liu Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical University Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease Capital Medical University

Aims:Hypercholesterolemia(HC) and inflammatory reaction are known to increase myocardial vulnerability to myocardial ischemia/reperfusion(MI/R) injury;however,the underlying mechanisms are not fully understood.The present study was designed to determine whether myeloperoxidase(MPO),an inflammatory cytokine expressed in cardiomyocytes following MI/R injury,exacerbated myocardial vulnerability to MI/R injury by interfering with the protective function of nitric oxide(NO) in HC rats.Methods:Male Wistar rats were fed either a normal or a high-cholesterol diet for 10 weeks,treated with vehicle or MPO inhibitor(ABAH,25.0 mg/kg/d for the last week),and subjected to MI/R(30 min/3 h or 24 h).MPO activity and distribution,cardiac function,serum LDH and CK level,myocardial infarct size,cardiomyocyte apoptosis,cardiac caspase-3 activity,NOx,nitrotyrosine(NT) level,iNOS expression,and cGMP content were assessed.Results:Compared with rats on a normal diet,MPO activity in MI/R hearts was significantly increased(1.33-fold;P <0.05).MPO immunostaining was not only observed in perivascular and extracellular spaces in MI/R hearts,but also in cardiomyocytes.This intra-cardiomyocyte MPO staining was further intensified by HC.We observed a strong positive correlation between cardiac MPO activity and LDH,CK,infarct size,apoptotic index,and caspase-3 activity,while there was a negative correlation between cardiac MPO activity and cardiac function.In HC rats MI/R tissue,the level of NOx and NT increased,the expression of iNOS increased,but the content of cGMP decreased.Treatment with ABAH significantly inhibited HC-induced MPO overexpression and activation,improved cardiac function,serum LDH and CK level,infarct size,myocardial cell apoptosis,MI/R injury,reduced NOx,NT,and iNOS,and increased cGMP.In addition,a scavenger of peroxynitrite(FeTMPyP) or iNOS inhibitor(1400 W) partially reversed MI/R injury in HC rats by lowering NT expression and MPO activity and raising the level of cGMP.Conclusion:Our results demonstrated that HC increased t

关键词： myeloperoxidase hypercholesterolemia myocardial ischemia/reperfusion injury myocardial vulnerability nitric oxide

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Serum myeloperoxidase Level in Systemic Lupus Erythematosus

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Chinese Medical Sciences Journal 2015年第3期30卷 199-202页

作者： Ming-jian Bai Jing Feng Feng Yu Cun-ling Yan Chan-juan Cui Lei Huang Zhen-ru Feng Department of Clinical Laboratory Aerospace Central Hospital Department of Nephrology Peking University First Hospital Department of Clinical Laboratory Peking University First Hospital

SYSTEMIC lupus erythematosus （SLE） is a systemicautoimmune disease. Several mechanismshave been put forward as underlying the loss ofself-tolerance and development of organdysfunction, such as genetic, environmental... 详细信息

关键词： myeloperoxidase systemic lupus erythematosus

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Clinical Significance of a myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第4期30卷 437-442页

作者：王燕颖王文多张艳霞赵欣杨东亮 Department of Gastroenterology Heilongjiang Provincial Hospital Department of Infectious Disease Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO–463 G/A genotype and its relationship with iNOS expression in a typical cell block from ascitic fluid were detected by immunohistochemistry and polymerase chain reaction-restricted fragment length polymorphism analysis (PCR-RFLP). In the HPS group, the partial pressure of oxygen in blood and ascitic fluid was significantly decreased (8.95±1.58 kPa and 6.81±0.95 kPa, respectively; both P<0.01), while the partial pressure of carbon dioxide significantly increased (4.62±0.20 kPa and 5.92±0.45 kPa, respectively; P<0.01). MPO and iNOS levels were significantly increased in the HPS group as compared with the non-HPS group. These increases were even more remarkable in ascitic fluid (41.36±11.62 and 13.23±4.81 μg/L; 10.27± 3.20 and 4.95±1.12 μg/L) than in blood (16.66±5.24 and 4.87±1.73 μg/L; 5.79±2.31 and 2.35±0.84 μg/L). The distribution of the MPO genotypes GG, GA, and AA were 76.2%, 22.2% and 1.6% in the HPS group, and 57.7%, 37.9% and 4.4% in the non-HPS group (P<0.05). The expression of iNOS was significantly higher in patients with the G alleles (G/G and G/A) (61.54%, 48/78) than in patients with A alleles (G/A and A/A) (38.46%, 30/78) (P<0.01). It was suggested that the expression levels of iNOS and MPO were correlated with HPS-induced hypoxemia. The MPO-463 G/A mutation might be a protective factor that prevents the development of HPS. The MPO might be involved in the regulation of iNOS expression. In humans, MPO pathways, the iNOS/NO system, and their interaction might have an impact on the occurrence and development of

关键词： hepatopulmonary syndrome myeloperoxidase inducible nitric oxide synthase polymorphism

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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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Pathogenic role of myeloperoxidase in acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2009年第6期8卷 627-631页

作者： Serge Chooklin Andriy Pereyaslov Ihor Bihalskyy Department of Surgery Medical University Lviv Ukraine

BACKGROUND:myeloperoxidase(MPO)has been implicated in promoting tissue damage in various inflammatory diseases.However,MPO blood levels in relation to the severity of acute pancreatitis(AP)and its time-course have not been studied.The present study aimed to determine the role of MPO in AP.METHODS:We studied 86 patients with AP(48 patients with mild and 38 with severe pancreatitis)and 18 controls(volunteers).The relations of serum MPO levels to cytokine level,severity,and time-course of pancreatitis were studied.The serum level of MPO and cytokines were measured by MPO-EIA and cytokines ELISA,respectively.RESULTS:The highest level of MPO was noted at the first day in patients with severe AP.A decrease of MPO blood level occurred during the first three days in all patients with necrotizing pancreatitis.The development of pancreatitis-associated lung injury and purulent complications was accompanied by increased MPO levels.Administration of pentoxifylline significantly reduced the MPO blood level,which was clearly correlated with the levels of proinflammatory cytokines in the two groups of patients.CONCLUSIONS:The results of the present study showed the MPO blood level is dependent on the severity of AP and on cytokine blood levels.Pentoxifylline in the complex management of severe AP may improve the results of treatment.

关键词： myeloperoxidase cytokines acute pancreatitis pentoxifylline

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Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide,glutathione peroxidase,and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2008年第11期3卷 1233-1236页

作者： Qingde Wang Guixiang Cui Hongxia Liu Yizhao Li Fengshan Wang Department of Neurology Hospital of Shandong Aluminium Industry Co.Ltd. Zibo 255069 Shandong Province China Department of Rehabilitation Qilu Hospital Shandong University Jinan 250012 Shandong Province China Heze Third People＇s Hospital Heze 274000 Shandong Province China Department of Rehabilitation Shandong Disabled Rehabilitation Center Jinan 250100 Shandong Province China Institute of Biochemistry and Biotechnique College of Pharmacy Shandong University Jinan 250012 Shandong Province China

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO a

关键词： cerebral ischemia/reperfusion nitric oxide myeloperoxidase glutathione peroxidase low molecular weight heparin-superoxide dismutase conjugate

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Clinical correlation between myeloperoxidase and acute coronary syndrome

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Journal of Geriatric Cardiology 2007年第4期4卷 209-212页

作者： Jie Wang Yanwei Xing Changsheng Ma Shihong Li Zhizhong Li Yonghong Gao Yibing Nong Guanganmen Hospital Chinese Academy of Traditionel Chinese Medical Beijing 100053 China Guanganmen Hospital Chinese Academy of Traditionel Chinese Medical Beijing 100053 China Anzhen Hospital Capital University of Medical Sciences Beijing 100029 China Anzhen Hospital Capital University of Medical Sciences Beijing 100029 China Anzhen Hospital Capital University of Medical Sciences Beijing 100029 China Dongzhimen Hospital Beijing 100700 China Dongfang Hospital Beijing 100701 China

Objective To study whether myeloperoxidase (MPO) can provide prognostic information in patients with acute coronary syndromes (ACS). Methods The study population consisted of 274 consecutive patients with ACS. All patients underwent coronary angiography which showed significant coronary artery disease and blood samples were collected at admission. Follow-ups were scheduled at 1, 3, and 6 months.The end point included cardiac death, acute myocardial infarction (MI), percutaneous or surgical revascularization. Results Patients with elevated MPO serum levels (MPO ≥ 72.2 AUU/L) were more likely to have diabetics and had a history of coronary events. Kaplan-Meier event rate curves with accumulative incidence of end point at 6-month follow-up in the MPO ≥ 72.2 AUU/L group was significantly higher than in MPO<72.2 AUU/L group. Conclusions MPO may be a powerful predictor of adverse outcome in patients with ACS.(J Geriatr Cardiol 2007;4:209-212)

关键词： myeloperoxidase acute coronary syndromes

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Severity evaluation value of serum myeloperoxidase content detection in patients with acute coronary syndrome

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Journal of Hainan Medical University 2017年第1期23卷 37-40页

作者： Zhao-Di Xie Qiang Wu Jian Huang Jing Lu Laboratory Department Qilian Community Health Service Centre of Dachang Town Baoshan District ShanghaiShanghai200444China Laboratory Department The Fifth Peopleˇs Hospital of ShanghaiFudan UniversityShanghai200240China

Objective:To analyze the value of serum myeloperoxidase content detection for severity evaluation in patients with acute coronary syndrome.Methods: Acute coronary syndrome (ACS) group included 32 cases, stable angina pectoris (SAP) group included 46 cases, levels of myeloperoxidase (MPO), inflammatory factors and lipid metabolism indexes in serum were compared, coronary echocardiography blood flow parameters were detected, and the correlation between MPO and ACS severity-associated indexes was further analyzed.Results:MPO content in serum of ACS group was significantly higher than those of SAP group and control group;inflammatory factors hs-CRP, IL-6, MCP-1 and LP-PLA2 content in serum were higher than those of SAP group and control group while IL-13 and TGFβ content were lower than those of SAP group and control group;lipid metabolism indexes TC, TG, LDL-C, ApoAI and ApoB content in serum were higher than those of SAP group and control group while HDL-C content was lower than that of SAP group and control group;ultrasonic coronary blood flow parameters SPV, DPV, A, CFVR and CTVⅠ levels were lower than those of SAP group and control group. The serum MPO content in patients with ACS was directly correlated with the content of inflammatory factors and lipid metabolism indexes as well as thelevels of coronary blood flow parameters.Conclusions:Serum MPO content in patients with ACS is directly correlated with the disease severity, and can be used as a reliable index for long-term guide of treatment and prediction of treatment outcome.

关键词： Acute coronary syndrome myeloperoxidase Lipid metabolism Inflammatory factors

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