A myeloperoxidase precursor, pro-myeloperoxidase, is present in human plasma and elevated in cardiovascular disease patients.

Myeloperoxidase (MPO)-derived oxidants have emerged as a key contributor to tissue damage in inflammatory conditions such as cardiovascular disease. Pro-myeloperoxidase (pro-MPO), an enzymatically active precursor of myeloperoxidase (MPO), is known to be secreted from cultured bone marrow and promyelocytic leukemia cells, but evidence for the presence of pro-MPO in circulation is lacking. In the present study, we used a LC-MS/MS in addition to immunoblot analyses to show that pro-MPO is present in human blood plasma.

Antiinflammatory and Antimicrobial Effects of Thiocyanate in a Cystic Fibrosis Mouse Model.

Thiocyanate (SCN) is used by the innate immune system, but less is known about its impact on inflammation and oxidative stress. Granulocytes oxidize SCN to evolve the bactericidal hypothiocyanous acid, which we previously demonstrated is metabolized by mammalian, but not bacterial, thioredoxin reductase (TrxR). There is also evidence that SCN is dysregulated in cystic fibrosis (CF), a disease marked by chronic infection and airway inflammation.

Ceruloplasmin is an endogenous inhibitor of myeloperoxidase.

Myeloperoxidase is a neutrophil enzyme that promotes oxidative stress in numerous inflammatory pathologies. It uses hydrogen peroxide to catalyze the production of strong oxidants including chlorine bleach and free radicals. A physiological defense against the inappropriate action of this enzyme has yet to be identified.

Factors influencing local and systemic levels of plasma myeloperoxidase in ST-segment elevation acute myocardial infarction.

Myeloperoxidase (MPO) is associated with risk in acute coronary syndromes. However, the precise role it plays in ST-elevation myocardial infarction (STEMI) remains unclear. In this study we tested the hypothesis that levels of MPO in plasma after a myocardial infarction are affected by its ability to bind to the endothelium and there is local release of the enzyme at the culprit lesion.

Increased thrombin-induced polymerization of fibrinogen associated with high protein carbonyl levels in plasma from patients post myocardial infarction.

Increased levels of protein carbonyls have been measured in plasma of patients following a myocardial infarction (Mocatta et al. J. Am.

The common G-866A polymorphism of the UCP2 gene and survival in diabetic patients following myocardial infarction.

Background: A variant in the promoter of the human uncoupling protein 2 (UCP2) gene, the G-866A polymorphism, has been associated with future risk of coronary heart disease events, in those devoid of traditional risk factors and in those suffering from diabetes. We thus examined the impact of the G-866A polymorphism on 5-year survival in a cohort of 901 post-myocardial infarction patients, and the impact of type-2 diabetes on this relationship. The association of UCP2 with baseline biochemical and hormonal measurements, including levels of the inflammatory marker myeloperoxidase, was also examined.

Extracellular amino acids and lipid peroxidation products in periventricular white matter during and after cerebral ischemia in preterm fetal sheep.

It is widely hypothesized that accumulation of excitatory amino acids, and oxygen free radicals during or after exposure to hypoxia-ischemia play a pivotal role in preterm periventricular white matter injury; however, there is limited evidence in the intact brain. In preterm fetal sheep (0.65 gestation; term 147 days) we found no significant increase in extracellular levels of excitatory amino acids measured by microdialysis in the periventricular white matter during cerebral ischemia induced by bilateral carotid occlusion.

Plasma concentrations of myeloperoxidase predict mortality after myocardial infarction.

Objectives: This study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI).

Background: Reactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes.

Methods: Detailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission.

Angiotensin type-1 receptor A1166C gene polymorphism correlates with oxidative stress levels in human heart failure.

Oxidative stress plays a critical role in the pathogenesis of cardiovascular disease and diabetes. Studies in vascular cells and experimental animals have demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation of reactive oxygen species by activating nicotinamide-adenine dinucleotide phosphate oxidases, but the relevance of this pathway to human heart disease has not been established. Here we demonstrate that a polymorphism in the AT1R gene (A1166C), linked to increased receptor activity, is associated with elevated levels of oxidative stress markers in heart failure patients but not in healthy controls.

Nuclear factor kappaB activation in pulmonary leukocytes from infants with hyaline membrane disease: associations with chorioamnionitis and Ureaplasma urealyticum colonization.

Unresolved pulmonary inflammation in hyaline membrane disease (HMD) may be a precursor to the development of chronic lung disease of early infancy. We investigated whether nuclear factor kappaB (NF-kappaB), a transcription factor that regulates the inflammatory process, is activated in pulmonary leukocytes in tracheal aspirates from premature infants with HMD. A total of 172 samples were obtained from 59 infants, two thirds of whom showed NF-kappaB activation in lung neutrophils and macrophages on at least one occasion.

The relationship of CSF and plasma cytokine levels to cerebral white matter injury in the premature newborn.

Ischemia and systemic infection are implicated in the etiology of periventricular white matter injury, a major cause of adverse motor and cognitive outcome in preterm infants. Cytokines are signaling proteins that can be produced as part of the inflammatory response to both ischemia and infection. The aim of this study was to relate cerebrospinal fluid (CSF) concentrations of IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) to magnetic resonance-defined white matter injury in preterm infants.

Myeloperoxidase and protein oxidation in the airways of young children with cystic fibrosis.

Cystic fibrosis (CF) is characterized by considerable oxidative stress. However, it is not known whether oxidative stress is an important feature early in this disease. We have investigated a group of infants and young children with CF to establish whether oxidants are produced in their airways.

The effect of gestational age and labour on markers of lipid and protein oxidation in cord plasma.

There are many potential sources of reactive oxidants around the time of birth and pre-term infants are considered to be particularly vulnerable to oxidative injury. To gain insight into these processes, we have measured biomarkers of lipid and protein oxidation in umbilical cord plasma and related concentrations to mode of delivery and gestational age. Protein carbonyls were measured by ELISA and malondialdehyde (MDA) by HPLC after reaction with thiobarbituric acid, for 54 pre-term (< or = 36 weeks gestational age) and 43 term infants.

Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury.

Free radical mediated cellular injury has been hypothesized to play a key role in the pathogenesis of white matter injury in the premature infant, although direct evidence is lacking. Between April 1999 and May 2001, 22 very low birthweight infants, 30 term infants, and 17 adults had samples of cerebrospinal fluid (CSF) collected for clinical indications. Only CSF samples without any evidence of meningeal inflammation were analyzed for the levels of the lipid peroxidation products, 8-isoprostane and malondialdehyde (MDA), and protein carbonyls as a measure of protein oxidation.

Markers of oxidative injury in the cerebrospinal fluid of a premature infant with meningitis and periventricular leukomalacia.

Free radicals have been hypothesized to play a key role in the evolution of periventricular leukomalacia, although direct evidence of oxidative injury in the human infant is lacking. This case report is the first to demonstrate a marked elevation in the levels of lipid and protein oxidative products in the cerebrospinal fluid during the evolution of periventricular leukomalacia in a premature infant with meningitis.