Role Of Myeloperoxidase Research Articles

Assessment of Myeloperoxidase and Nitric Levels around Dental Implants and Natural Teeth as a Marker of Inflammation: A Comparative Study

Dental implants form the mainstay of dental treatment involving rehabilitation of missing teeth. One of the major concerns for the clinicians doing dental implants is the postsurgical failure of dental implants. Success of dental implants is dependent upon the skills of the surgeon and the amount and quality of the bone remaining at the edentulous area where dental implant has to be placed. Myeloperoxidase (MPO) and nitrites are few of the enzymes and molecules which are said to be altered in inflammation. However, their exact role in the inflammatory processes around natural tooth and dental implant is still unclear. Hence we comparatively evaluated the levels of MPO and nitrites in the areas around the dental implants and natural teeth. The present study comprises 42 patients who underwent prosthetic rehabilitation by dental implants from 2011 to 2014. Depth of probing value (DP), score of plaque index (SPI), gingival index (GI), and index of gingival bleeding time (GBT) were evaluated for the assessment of the periimplant soft tissue changes. Assessment of inflammation around the dental implant surface and around natural tooth was done based on the readings of these parameters. For the measurement of the MPO levels, spectrophotometric MPO assay was used. All the results were analyzed by Statistical Package for the Social Sciences (SPSS) software. The mean plaque index values were 1.56 and 0.97 in periodontitis cases of natural teeth and inflamed cases of dental implants respectively. While comparing mean plaque index, mean probing depth, and mean gingival bleeding index in between the two groups, significant difference was obtained. Mean MPO concentration in periodontitis and gingivitis cases in natural teeth were 0.683 and 0.875 U/μL, while in inflamed dental implant cases, the mean value was 0.622 U/μL. While comparing the total MPO levels, total nitrite levels, and total nitrite concentration in between two study groups, significant difference was obtained. On comparing the healthy and periodontitis cases in natural teeth, significant difference was obtained. In the inflammatory processes occurring around dental implant and natural teeth, MPO and NO make some amount of significant contribution. The present study enforces on the role of MPO and nitrite as diagnostic and prognostic marker.

Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: Role of myeloperoxidase and arylamine free radicals

In this study, the cellular effects resulting from the metabolism of aminoglutethimide by myeloperoxidase were investigated. Human promyelocytic leukemia (HL-60) cells were treated with aminoglutethimide (AG), an arylamine drug that has a risk of adverse drug reactions, including drug-induced agranulocytosis. HL-60 cells contain abundant amounts of myeloperoxidase (MPO), a hemoprotein, which catalyzes one-electron oxidation of arylamines using H2O2 as a cofactor. Previous studies have shown that arylamine metabolism by MPO results in protein radical formation. The purpose of this study was to determine if pathways associated with a toxic response could be determined from conditions that produced protein radicals. Conditions for AG-induced protein radical formation (with minimal cytotoxicity) were optimized, and these conditions were used to carry out proteomic studies. We identified 43 proteins that were changed significantly upon AG treatment among which 18 were up-regulated and 25 were down-regulated. The quantitative proteomic data showed that AG peroxidative metabolism led to the down-regulation of critical anti-apoptotic proteins responsible for inhibiting the release of pro-apoptotic factors from the mitochondria as well as cytoskeletal proteins such as nuclear lamina. This overall pro-apoptotic response was confirmed with flow cytometry which demonstrated apoptosis to be the main mode of cell death, and this was attenuated by MPO inhibition. This response correlated with the intensity of AG-induced protein radical formation in HL-60 cells, which may play a role in cell death signaling mechanisms.

Serum and salivary myeloperoxidase in oral squamous cell carcinoma: A preliminary study

Background: Free radical damage to biologic molecules forms a basis for cancer development. Since DNA damage and methylation states are influenced by oxidative species catalyzed by myeloperoxidase (MPO), this enzyme is postulated to have a role in the occurrence of cancer. MPO has been studied in cancers such as those of the lung, ovary, and breast. However, serum and salivary studies of MPO in oral cancer are lacking. Aims: (1) To determine the MPO levels in the serum and saliva of patients with primary oral squamous cell carcinoma (OSCC). (2) To compare and correlate the serum and salivary MPO levels in patients with primary OSCC and healthy controls. Subjects and Methods: A total of 30 subjects were involved in this study, of which study group consisted of 15 subjects and control group consisted of 15 subjects. Study group included subjects with histologically proven primary OSCC. Serum and salivary samples were collected from all the subjects. Results: The results showed that the serum levels of MPO were slightly higher in the study group as compared to the control group; however, the difference was not significant. In saliva, levels of MPO were slightly lower in the study group as compared to the control group. The difference was not significant. Conclusions: This study could not find a significant correlation between serum and salivary MPO and OSCC. However, our study consisted of a limited number of samples and as such can be considered a pilot study. Studies with larger sample size are needed to give better insight into the role of MPO in OSCC.

Emerging Role of Myeloperoxidase in the Prognosis of Nephrotic Syndrome Patients Before and After Steroid Therapy.

Myeloperoxidase (MPO) is a myelocyte derived iron containing enzyme particularly involved in host defense by destroying foreign micro organisms invading the body. Numerous evidences suggest that MPO is involved in the pathogenesis of many inflammatory diseases, especially atherosclerosis. Present study deals with the role of MPO in the renal function and progression of disease in Nephrotic syndrome patients. Case- Control Study carried out in Kasturba Medical College Hospital, Mangalore, India. Forty newly diagnosed Nephrotic syndrome cases, 40 age and sex matched healthy controls and 15 subjects in Nephrotic syndrome remission, were included in the study. Myeloperoxidase enzyme was assayed by 4 amino antipyrine methods in all the subjects. Other renal parameters like urea, creatinine, Blood Urea Nitrogen (BUN), BUN- Creatinine ratio (BUN/Cr) total protein, albumin, globulin, albumin - globulin ratio (A/G ratio) and estimated Glomerular Filtration Rate (eGFR) were also analysed. 24 hour urine protein-creatinine ratio was estimated in Nephrotic syndrome cases and remission group by turbidimetric assay. Students paired t-test and Wilcoxon Signed Rank test were used for the comparison of the data. Pearson and Spearman analyses were used for correlation of the parameters. MPO levels were found to be high in Nephrotic syndrome cases when compared to healthy controls. Urea, creatinine, BUN, BUN/Cr ratio and eGFR were high in Nephrotic syndrome cases while total protein, albumin, globulin and A/G ratio showed decreased levels. MPO had a positive correlation with creatinine and urine protein-creatinine ratio in Nephrotic syndrome. During remission, MPO levels decreased significantly while total protein and albumin levels increased. Myeloperoxidase enzyme is found to be elevated and it strongly correlated with the severity of disease in Nephrotic syndrome. Further studies can be done to use MPO as a therapeutic target in Nephrotic syndrome to ameliorate the symptoms.

86 - Role of Myeloperoxidase in the Modulation of Cellular Lysosomal Cathepsin Protease Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?

86 - Role of Myeloperoxidase in the Modulation of Cellular Lysosomal Cathepsin Protease Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?

Increased A3AR-dependent vasoconstriction in diabetic mice is promoted by myeloperoxidase.

Vascular dysfunction importantly contributes to mortality and morbidity in various cardiac and metabolic diseases. Among endogenous molecules regulating vascular tone is adenosine, with the adenosine A3 receptor (A3AR) exerting cardioprotective properties in ischemia and reperfusion. However, overexpression of A3AR is suggested to result in vascular dysfunction and inflammation. The leukocyte enzyme myeloperoxidase (MPO) is an important modulator of vascular function with nitric oxide-consuming and proinflammatory properties. Increased MPO plasma levels are observed in patients with cardiovascular disorders like heart failure, acute coronary syndromes, and arrhythmias. Given that vascular dysfunction and inflammation are also hallmarks of diabetes, the role of MPO in adenosine-dependent vasomotor function was investigated in a murine model of diabetes mellitus. Wild-type (WT) and MPO-deficient (Mpo) mice were treated with Streptozotocin (STZ), which induced an increase of MPO plasma levels in WT mice and led to enhanced aortic superoxide generation as assessed by dihydroethidium staining in STZ-treated WT mice as compared with controls. The vasoconstriction of aortic segments in response to the A3AR agonist Cl-IB-MECA (2-Chloro-N6-(3-iodobenzyl)-N-methyl-5-carbamoyladenosine) as determined by isometric force measurements was augmented in diabetic WT as compared with diabetic Mpo mice. Moreover, A3AR protein expression was enhanced in STZ-treated mice but was attenuated by MPO deficiency. The current data reveal an MPO-mediated increase of vascular A3AR expression under diabetic conditions, which leads to enhanced vasoconstriction in response to A3AR agonists and discloses an additional mechanism of MPO-mediated vascular dysfunction.

Recent Patents on Oxidative Stress-Related Biomarkers in Chronic Heart Failure: The Central Role of Endothelium and Myeloperoxidase

Endothelial cells are key modulators of multiple physiological processes, and their impairment may result in the generation of endothelial dysfunction and ultimately cardiovascular diseases. Under physiologic conditions, reactive oxygen and nitrogen mediators of endothelial cells act to propagate signals driven by different stimuli, by forming molecules with a longer half-life like hydrogen peroxide. Reactive oxygen species (ROS) are constantly produced as a consequence of aerobic metabolism. Under physiologic conditions, their tendency to cause oxidative damage is counterbalanced by the action of antioxidants or oxidant-scavenging enzymes. An imbalance in favour of oxidants leads to oxidative stress, which can result in cardiomyocyte apoptosis and reduced bioavailability of vascular nitric oxide (NO). Together, these processes may lead to altered vasodilatation of the coronary, pulmonary and peripheral vascular beds. Myeloperoxidase is a key enzyme, capable of impairing intracellular NO reservoirs as well as producing oxidized amino acids such as 3-chlorotyrosine or 3-nitrotyrosine. Recent literature data have shown that apart neutrophils, this enzyme may be expressed by other cell types, and remarkably by endothelial cells both in vitro and in vivo, as a consequence of the exposure to oxidative stress. In this review we analyze recent literature and patents related to the detection, quantification and role of myeloperoxidase as a biomarker in patients affected by chronic heart failure or other cardiovascular diseases. A particular focus is given to analytical approaches aimed to detect early signals of variations in ROS or related enzymes or their by-products, via serological or other low-invasivity assays. The developments in this field may constitute a key improvement of the ability to manage and treat patients suffering from CHF as well as allowing to elucidate the molecular mechanisms behind the clinical phenomena.

(−)-Epicatechin regenerates the chlorinating activity of myeloperoxidase in vitro and in neutrophil granulocytes

The heme-containing enzyme myeloperoxidase (MPO) is mainly expressed in polymorphonuclear leukocytes (PMNs), the most abundant immune cell type in the blood. Accordingly, MPO is classically attributed to the innate immune response against pathogens. Yet, new results also show immune-regulatory functions of the halogenating MPO activity including the formation of anti-inflammatory mediators. In this work we tested the ability of the flavonoid (−)-epicatechin to regenerate this enzymatic activity both in vitro at the isolated MPO–H2O2–Cl− system and ex vivo in human PMNs. For all experiments the non-fluorescent dye aminophenyl fluorescein (APF) was used. Upon oxidation by the MPO, the halogenation product hypochlorous acid (HOCl) fluorescein is formed which can be detected e.g. by flow cytometry. The in vitro- and ex vivo-results concordantly show that (−)-epicatechin is a suitable substrate to overcome a compound II accumulation of MPO which was experimentally forced by applying excess hydrogen peroxide. Thereby concentration-dependent effects of the flavan-3-ol were found in both cases and confirmed the proposed mode of action of (−)-epicatechin. The results are in accordance with previous stopped-flow kinetic studies which showed a high reactivity of the polyphenol with MPO compound II. The obtained data may contribute to the explanation of the well-known health promoting effects of (−)-epicatechin. Moreover, the presented study provides new insights into the role of MPO during inflammation.

Carbamylation of LDL and its relationship with myeloperoxidase in Type 2 diabetes mellitus

LDL (low-density lipoprotein) is subjected to pro-atherogenic modifications in the circulation. A novel uraemia-independent mechanism of carbamylation of lipoproteins mediated by MPO (myeloperoxidase) has recently been reported. We have investigated whether carbamylation of LDL was increased in patients with Type 2 diabetes without renal impairment and the role of MPO. cLDL (carbamylated LDL) and MPO were measured by ELISA in a cross-sectional study of 198 patients and 174 non-diabetic controls. The impact of lowering MPO on plasma cLDL was determined by assaying cLDL and MPO in archived samples from a previous randomized open-label parallel group study comparing rosiglitazone (n=20) and sulfonylurea (n=24). Both plasma cLDL (P<0.05) and MPO levels (P<0.01) were higher in patients with Type 2 diabetes than controls in the cross-sectional study. Plasma cLDL correlated with MPO (r=0.42 and P<0.01) in subjects with diabetes, and plasma MPO was an independent determinant of plasma cLDL even after adjusting for age, gender, BMI (body mass index), apoB (apolipoprotein B), urea and HbA1c (glycated haemoglobin). In the randomized trial, rosiglitazone significantly lowered MPO (P<0.01) and cLDL (P<0.05), whereas no changes were observed in the sulfonylurea group despite a similar reduction in HbA1c. The magnitude of reduction in plasma cLDL correlated with changes in MPO, but not with HbA1c in the rosiglitazone group, suggesting that lowering MPO reduced plasma cLDL. Plasma cLDL is increased in patients with Type 2 diabetes even in the absence of renal impairment and carbamylation of LDL in these subjects is mainly mediated by MPO and not by urea.

The role of myeloperoxidase (MPO) for prognostic evaluation in sensitive cardiac troponin I negative chest pain patients in the emergency department

The diagnostic work-up of patients with acute chest pain in the emergency department (ED) is a challenging task. Serial troponin testing is required to rule-out acute myocardial infarction. To evaluate the value of myeloperoxidase (MPO) testing in sensitive cardiac troponin I (cTnI) negative patients with suspected acute coronary syndromes (ACS) in the routine setting of an ED. MPO was assessed in 432 consecutive patients presenting to the ED with ACS. In 266 patients, serial blood samples were available. After 6 weeks, major adverse cardiac events (MACE) were assessed. MPO and cTnI were measured in all available samples. For cTnI, a sensitive assay was used. Cut-off values were derived from an independent sample of 300 healthy volunteers. Incidence of MACE in our population was 13%. MPO levels revealed sensitivity (Sens) of 82.1% and specificity (Spec) of 37.2% for MACE compared with 60.7% Sens and 61.4% Spec for sensitive cTnI. In serial sensitive cTnI negative patients (n=218), MACE incidence was 6.4%. MPO continued to demonstrate significant discriminatory power for the prognosis of MACE. Multivariate analyses confirmed these findings. MPO has an independent prognostic value overall and most notably in patients tested negative with a higher sensitive cardiac troponin I assay. MPO could be a promising biomarker for the initial evaluation of patients in chest pain units and is worth further investigation.

The role of myeloperoxidase and myeloperoxidase–antineutrophil cytoplasmic antibodies (MPO-ANCAs) in the pathogenesis of human MPO-ANCA-associated glomerulonephritis

It is well known that antineutrophil cytoplasmic antibodies (ANCAs) are pathogenic and have a diagnostic value for ANCA-associated vasculitis. We demonstrated that a rise in myeloperoxidase (MPO)-ANCA titers during remission is often predictive of a future relapse in MPO-ANCA-associated vasculitis. Pathological examination of renal biopsies indicated that not only MPO-ANCAs, but also extracellular MPO, an in situ immune complex composed of MPO and MPO antibodies, may play important roles in the pathogenesis of glomerular capillary injury in MPO-ANCA-associated vasculitis.

Myeloperoxidase and Atherosclerosis

Myeloperoxidase (MPO), a member of the peroxidase family, emerged as a major player in the initiation and propagation of atherosclerotic cardiovascular disease (CVD). Evidence for its role in atherosclerosis include that MPO: a) induces endothelial dysfunction, b) modifies physiologically functional high density lipoprotein (HDL) into “dysfunctional HDL”, c) converts low density lipoprotein (LDL) into more atherogenic modified LDL form, and d) induces endothelial cell death and tissue factor expression involved in plaque vulnerability. Elevated levels of blood MPO are associated with CVD, predict incident risks for myocardial infarction and cardiac death in subjects with acute coronary syndrome, and predict future risk of coronary artery disease (CAD) in healthy individuals. In this article, we review current understandings on the role of MPO in pathophysiological processes involved in atherosclerosis and CVD.

Increased Myeloperoxidase Expression is Associated with Increase in Intra-Plaque Hemorrhage, Iron Content, Inflammation and Neovascularization in Diabetic Atherosclerosis: Implications for Plaque Progression

Background: Myeloperoxidase (MPO), a heme peroxidase enzyme produced by macrophages, is a marker of oxidative stress associated with increased cardiovascular events in Diabetes Mellitus (DM). In this study we hypothesize that MPO protein and gene expression is associated with increased Intra-Plaque Hemorrhage (IPH), iron deposition, plaque inflammation and neovascularization in DM atheroma. Methods: Twenty-six human aortas with advanced plaques (14 DM vs.12 No-DM) were studied. MPO protein and gene expression were quantified with immunohistochemistry and RT-PCR respectively. IPH was evaluated using H&E stain. Plaque iron was scored using Perl’s stain and graded Inflammatory cells and neovessels were manually counted in parallel sections using with (CD68 and CD3), and (CD34) using immunohistochemistry method. Results: Total plaque MPO protein expression density (973.13 ± 28.32 vs. 356.24 ± 26.95; p = 0.0001) and MPO gene expression (0.00267 ± 0.0007 vs. 0.00033 ± 0.0001; p = 0.0001), IPH percentage (57.1% vs. 16.7 %; p= 0.04), iron grade (0.79 ± 0.21 vs. 0.25 ± 0.13; p = 0.05), inflammatory cell grade (1.71 ± 0.10 vs. 1.17 ± 0.11; p = 0.001) and total neovessel content (48.96 ± 4.68 vs. 21.54 ± 2.27; p = 0.0001) were significantly increased in DM plaques when compared to no-DM. Conclusion: Increased MPO protein and gene expression are associated with a parallel increase in IPH, iron grade, inflammation grade and neovessel content in DM. This suggests a possible role of MPO in enhancing the IPH, iron deposition; inflammation and neovascularization in high risk DM plaques may possibly due to oxidative stress.

Functional Activity of Neutrophils in Diabetes Mellitus and Coronary Heart Disease: Role of Myeloperoxidase in the Development of Oxidative Stress

We performed a comparative analysis of functional activity of neutrophils in patients with type 2 diabetes mellitus with and without symptoms of CHD. Enhanced H2O2 production by neutrophils in response to N-formyl-Met-Leu-Phe (fMLP) was found in patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus associated with CHD, fMLP-induced release of myeloperoxidase from azurophilic granules of neutrophils was reduced and plasma myeloperoxidase level was elevated. Increased peroxidase activity of myeloperoxidase, reduced plasma catalase activity, and increased levels of TBA-reactive lipid peroxidation products and oxidized glutathione were detected in patients of both groups. Since myeloperoxidase is an important neutrophilic mediator of oxidative stress, its increased activity in the blood can be an additional marker of oxidative stress and cardiovascular risk in patients with diabetes mellitus.

Amniotic fluid myeloperoxidase in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine amniotic fluid myeloperoxidase concentration in women with preterm prelabor rupture of the membranes with microbial invasion of the amniotic cavity and histological chorioamnionitis. Methods: One hundred eighty-one women with singleton pregnancies with a gestational age between 24+0 and 36+6 weeks were included in this study. Amniocenteses were performed, and myeloperoxidase concentration in the amniotic fluid was determined using ELISA. Result: Women with microbial invasion of the amniotic cavity had higher median myeloperoxidase concentration than women without this condition (149.2 ng/mL vs. 54.6 ng/mL; p = 0.0006). Women with the presence of histological chorioamnionitis had higher median myeloperoxidase concentration than women without histological chorioamnionitis (103.7 ng/mL vs. 50.0 ng/mL; p = 0.0001). The presence of both microbial invasion of the amniotic cavity and histological chorioamnionitis was associated with higher median myeloperoxidase concentration (456.0 ng/mL vs. 52.9 ng/mL; p < 0.0001). The results remained significant after adjusting for gestational age. Conclusions: Increased amniotic fluid myeloperoxidase in microbial invasion of the amniotic cavity and histological chorioamnionitis confirm a role of myeloperoxidase in preterm prelabor rupture of the membranes pathophysiology.

A Novel Role for Myeloperoxidase in the Induction of C/EBP-Homologous Protein (CHOP)

A Novel Role for Myeloperoxidase in the Induction of C/EBP-Homologous Protein (CHOP)

A novel role of myeloperoxidase in the induction of endoplasmic reticulum (ER) stress

A novel role of myeloperoxidase in the induction of endoplasmic reticulum (ER) stress

Role of myeloperoxidase in relationship between smoking and risk of pancreatic cancer

Role of myeloperoxidase in relationship between smoking and risk of pancreatic cancer

Increased myeloperoxidase activity is a risk factor for ischemic heart disease in patients with diabetes mellitus

Using a previously developed spectrophotometric method (Bioorg. Khim. 2009, vol. 35, pp. 629–639) a significant increase of myeloperoxidase (MPO) activity (versus healthy control) was found in blood plasma of patients with type 2 diabetes mellitus (DM2) without cardiovascular complications, and also in patients with ischemic heart disease (IHD). The plasma MPO concentration measured by an enzyme-linked immunosorbent assay was significantly higher only in blood plasma of patients with DM2 and IHD. A significant positive correlation between blood MPO activity and blood MPO content was observed only in blood plasma samples from healthy donors. Increased MPO activity did not correlate with MPO concentration in blood plasma of patients with DM2 and DM2 with IHD. Taken together, these results indicate that studies on the MPO role in the development of pathological processes should include simultaneous determination of both the amount of enzyme and its peroxidase activity in blood of patients. The proposed approach gives comprehensive information about the relationship between MPO activity and MPO concentration in patient’s blood. Since the high concentration of MPO is a diagnostically important parameter for the prediction of development of endothelial dysfunction and cardiovascular diseases, the obtained results point to the contribution of MPO-dependent reactions in cardiovascular complications associated with diabetes mellitus. MPO activity may serve as an additional diagnostic criterion for determination of risk of IHD in DM patients.

Current role of myeloperoxidase in routine clinical practice

Recognition of inflammation as a critical contributor to atherothrombosis has led to the pursuit of new approaches for the diagnosis and treatment of patients with coronary heart disease. As the intricate relationships between cellular and noncellular participants in the inflammatory aspects of atherogenesis, plaque destabilization and thrombosis have been defined, specific constituents have emerged as potential noninvasive indicators of these processes. Myeloperoxidase is a protein released during degranulation of neutrophils and monocytes. The available experimental and epidemiologic data provide compelling evidence to sustain strong interest in myeloperoxidase as a candidate for clinical application. Nevertheless, additional investigation will be important to fully evaluate myeloperoxidase as a sensitive predictor for myocardial infarction in patients with chest pain.