Abstract
BACKGROUND AND AIMS:
METHODS:
CONCLUSIONS:
J Trace Elem Med Biol. 2016 Nov 23. pii: S0946-672X(16)30297-8. doi: 10.1016/j.jtemb.2016.11.007.
Correlations between ceruloplasmin, lactoferrin and myeloperoxidase in meconium
J Trace Elem Med Biol. 2016 Nov 23. pii: S0946-672X(16)30297-8. doi: 10.1016/j.jtemb.2016.11.007.
Myeloperoxidase and oxidative stress in rheumatoid arthritis
Myeloperoxidase and oxidative stress in rheumatoid arthritis
Objective. To determine whether MPO contributes to oxidative stress and disease activity in rheumatoid arthritis ( RA) and whether it produces hypochlorous acid in SF.
Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry.
Results. Plasma Myeloperoxidase concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2–14.2; P < 0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤3.2) (HDA 27.9 ng/ml, 20.2–34.1 vs LDA 22.1 ng/ml, 16.9–34.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4–2433.0 vs 30.2 ng/ml, IQR 25.1–50.9; P < 0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3-chlorotyrosine (r = 0.66; P = 0.003).
Conclusion. MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.
Lisa K. Stamp1, Irada Khalilova2, Joanna M. Tarr3, Revathy Senthilmohan2, Rufus Turner2, Richard C. Haigh3,4, Paul G. Winyard3 and Anthony J. Kettle2
+ Author Affiliations
1Department of Medicine, 2Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand, 3Peninsula Medical School, University of Exeter and 4Royal Devon and Exeter Foundation Trust, Exeter, UK.
Correspondence to: Lisa K. Stamp, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand. E-mail: lisa.stamp@cdhb.govt.nz
Objective. To determine whether MPO contributes to oxidative stress and disease activity in rheumatoid arthritis ( RA) and whether it produces hypochlorous acid in SF.
Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry.
Results. Plasma Myeloperoxidase concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2–14.2; P < 0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤3.2) (HDA 27.9 ng/ml, 20.2–34.1 vs LDA 22.1 ng/ml, 16.9–34.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4–2433.0 vs 30.2 ng/ml, IQR 25.1–50.9; P < 0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3-chlorotyrosine (r = 0.66; P = 0.003).
Conclusion. MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.
Lisa K. Stamp1, Irada Khalilova2, Joanna M. Tarr3, Revathy Senthilmohan2, Rufus Turner2, Richard C. Haigh3,4, Paul G. Winyard3 and Anthony J. Kettle2
+ Author Affiliations
1Department of Medicine, 2Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand, 3Peninsula Medical School, University of Exeter and 4Royal Devon and Exeter Foundation Trust, Exeter, UK.
Correspondence to: Lisa K. Stamp, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand. E-mail: lisa.stamp@cdhb.govt.nz
Myeloperoxidase Improves Risk Stratification in Patients with Ischemia and Normal Cardiac Troponin I Concentrations
BACKGROUND: We assessed the ability of myeloperoxidase (MPO) to identify the risk for major adverse cardiac events (MACE) in patients who present with ischemic symptoms suggestive of acute coronary syndrome and have a normal cardiac TROPONIN I (cTnI) value.
METHODS: We used Siemens (n = 400) and Abbott (n = 350) assays to measure MPO and cTnI in plasma samples from 400 patients. Event rates (myocardial infarction, cardiac death, percutaneous coronary intervention, coronary artery bypass grafting) were estimated by the Kaplan–Meier method and compared with the log-rank statistic.
RESULTS: At the 30-day follow-up, the adjusted hazard ratios for MACE were 3.9 (P < 0.001) for increased cTnI and 2.7 (P = 0.006) for increased MPO for the Siemens assays and were 5.5 (P < 0.001) for increased cTnI and 2.9 (P = 0.001) for increased MYELOPEROXIDASE for the Abbott assays. Similar findings were observed with 6 months of follow-up. Patients who initially had a normal cTnI value and an increased Siemens MPO value demonstrated a higher rate of MACE at 30 days than those in whom both values were normal (16.1% vs 3.6%, P = 0.002) and 6 months (18.1% vs 5.0%, P = 0.002). Similarly, patients who had an increased Abbott MPO result demonstrated a higher MACE rate at 30 days (12.3% vs 3.9%, P = 0.03) and at 6 months (16.2% vs 5.1%, P = 0.01) than those with normal values.
CONCLUSIONS: A combination of MPO and cTnI allowed the identification of a greater proportion of patients at risk for MACE than the use of cTnI alone. Increased MPO values remained predictive of future cardiac events even when the cTnI value was normal.
Received for publication October 13, 2010.
Accepted for publication January 7, 2011.
© 2011 The American Association for Clinical Chemistry
METHODS: We used Siemens (n = 400) and Abbott (n = 350) assays to measure MPO and cTnI in plasma samples from 400 patients. Event rates (myocardial infarction, cardiac death, percutaneous coronary intervention, coronary artery bypass grafting) were estimated by the Kaplan–Meier method and compared with the log-rank statistic.
RESULTS: At the 30-day follow-up, the adjusted hazard ratios for MACE were 3.9 (P < 0.001) for increased cTnI and 2.7 (P = 0.006) for increased MPO for the Siemens assays and were 5.5 (P < 0.001) for increased cTnI and 2.9 (P = 0.001) for increased MYELOPEROXIDASE for the Abbott assays. Similar findings were observed with 6 months of follow-up. Patients who initially had a normal cTnI value and an increased Siemens MPO value demonstrated a higher rate of MACE at 30 days than those in whom both values were normal (16.1% vs 3.6%, P = 0.002) and 6 months (18.1% vs 5.0%, P = 0.002). Similarly, patients who had an increased Abbott MPO result demonstrated a higher MACE rate at 30 days (12.3% vs 3.9%, P = 0.03) and at 6 months (16.2% vs 5.1%, P = 0.01) than those with normal values.
CONCLUSIONS: A combination of MPO and cTnI allowed the identification of a greater proportion of patients at risk for MACE than the use of cTnI alone. Increased MPO values remained predictive of future cardiac events even when the cTnI value was normal.
Received for publication October 13, 2010.
Accepted for publication January 7, 2011.
© 2011 The American Association for Clinical Chemistry
Current role of myeloperoxidase in routine clinical practice
Abstract:
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.
Expert Review of Cardiovascular Therapy, Volume 9, Number 2, February 2011 , pp. 223-230(8)
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.
Expert Review of Cardiovascular Therapy, Volume 9, Number 2, February 2011 , pp. 223-230(8)
Myeloperoxidase, inflammation, and dysfunctional high-density lipoprotein
Abstract
High-density lipoprotein (HDL) has many protective activities against atherosclerosis, including its role in reverse cholesterol transport, and its antioxidant, anti-inflammatory, and endothelial cell maintenance functions. However, all HDL is not functionally equivalent. The authors of recent studies have shown that infection, inflammation, diabetes, and coronary artery disease are associated with dysfunctional HDL. HDL can lose its protective activities through a variety of mechanisms, including, but not limited to, altered protein composition, oxidative protein modification mediated by the enzyme myeloperoxidase, and lipid modification. Studies in which the authors used bacterial endotoxin in humans and mice have directly demonstrated changes in HDL composition, loss of HDL’s cholesterol acceptor activity, and decreased hepatic processing and secretion of cholesterol. Although a routine clinical assay for dysfunctional HDL is not currently available, the development of such an assay would be beneficial for a better understanding of the role that dysfunctional HDL plays as a risk factor for coronary artery disease and for the determination of how various drug therapies effect HDL functionality.
Journal of Lipidology: Volume 4, Issue 5, Pages 382-388 (September 2010)
High-density lipoprotein (HDL) has many protective activities against atherosclerosis, including its role in reverse cholesterol transport, and its antioxidant, anti-inflammatory, and endothelial cell maintenance functions. However, all HDL is not functionally equivalent. The authors of recent studies have shown that infection, inflammation, diabetes, and coronary artery disease are associated with dysfunctional HDL. HDL can lose its protective activities through a variety of mechanisms, including, but not limited to, altered protein composition, oxidative protein modification mediated by the enzyme myeloperoxidase, and lipid modification. Studies in which the authors used bacterial endotoxin in humans and mice have directly demonstrated changes in HDL composition, loss of HDL’s cholesterol acceptor activity, and decreased hepatic processing and secretion of cholesterol. Although a routine clinical assay for dysfunctional HDL is not currently available, the development of such an assay would be beneficial for a better understanding of the role that dysfunctional HDL plays as a risk factor for coronary artery disease and for the determination of how various drug therapies effect HDL functionality.
Journal of Lipidology: Volume 4, Issue 5, Pages 382-388 (September 2010)
Myeloperoxidase, inflammation, and dysfunctional high-density lipoprotein
Abstract
High-density lipoprotein (HDL) has many protective activities against atherosclerosis, including its role in reverse cholesterol transport, and its antioxidant, anti-inflammatory, and endothelial cell maintenance functions. However, all HDL is not functionally equivalent. The authors of recent studies have shown that infection, inflammation, diabetes, and coronary artery disease are associated with dysfunctional HDL. HDL can lose its protective activities through a variety of mechanisms, including, but not limited to, altered protein composition, oxidative protein modification mediated by the enzyme myeloperoxidase, and lipid modification. Studies in which the authors used bacterial endotoxin in humans and mice have directly demonstrated changes in HDL composition, loss of HDL’s cholesterol acceptor activity, and decreased hepatic processing and secretion of cholesterol. Although a routine clinical assay for dysfunctional HDL is not currently available, the development of such an assay would be beneficial for a better understanding of the role that dysfunctional HDL plays as a risk factor for coronary artery disease and for the determination of how various drug therapies effect HDL functionality.
Journal of Lipidology: Volume 4, Issue 5, Pages 382-388 (September 2010)
High-density lipoprotein (HDL) has many protective activities against atherosclerosis, including its role in reverse cholesterol transport, and its antioxidant, anti-inflammatory, and endothelial cell maintenance functions. However, all HDL is not functionally equivalent. The authors of recent studies have shown that infection, inflammation, diabetes, and coronary artery disease are associated with dysfunctional HDL. HDL can lose its protective activities through a variety of mechanisms, including, but not limited to, altered protein composition, oxidative protein modification mediated by the enzyme myeloperoxidase, and lipid modification. Studies in which the authors used bacterial endotoxin in humans and mice have directly demonstrated changes in HDL composition, loss of HDL’s cholesterol acceptor activity, and decreased hepatic processing and secretion of cholesterol. Although a routine clinical assay for dysfunctional HDL is not currently available, the development of such an assay would be beneficial for a better understanding of the role that dysfunctional HDL plays as a risk factor for coronary artery disease and for the determination of how various drug therapies effect HDL functionality.
Journal of Lipidology: Volume 4, Issue 5, Pages 382-388 (September 2010)
Subscribe to:
Posts (Atom)