The Experts below are selected from a list of 7152 Experts worldwide ranked by ideXlab platform
Rudi Busse - One of the best experts on this subject based on the ideXlab platform.
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Abstract —Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox−/−, and endothelial NO synthase (eNOS)−/− mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS−/− mice, but was attenuated in segments from gp91phox−/− mice. Endothelium-dependent relaxation was greater in aortae from gp91phox−/− than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox−/− mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO. ( Circ Res. 2000;87:26-32.)
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox(-/-), and endothelial NO synthase (eNOS)(-/-) mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS(-/-) mice, but was attenuated in segments from gp91phox(-/-) mice. Endothelium-dependent relaxation was greater in aortae from gp91phox(-/-) than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox(-/-) mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO.
Ellen Mcerlean - One of the best experts on this subject based on the ideXlab platform.
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prognostic value of myeloperoxidase in patients with chest pain
Obstetrical & Gynecological Survey, 2004Co-Authors: Marie Luise Brennan, Ronnier J. Aviles, Michael Pepoy, Mehdi H Shishenbor, Vijay Nambi, Frederick Van Lente, Marc S. Penn, Marlene Goormastic, Ellen McerleanAbstract:The entire process of arterial plaque formation has been linked with inflammation, and extensive infiltration of neutrophils and monocytes is observed in thrombosed plaque in patients with acute coronary disease. One possible means by which Leukocytes could influence the stability of plaque is myeloperoxidase, a Leukocyte Enzyme that is present in elevated amounts in patients with cardiovascular disease. This study examined the possibility that plasma levels of myeloperoxidase might serve as a marker of plaque vulnerability in patients seen in the emergency department with chest pain. The study group included 604 such patients, seen sequentially, whose most frequent final diagnoses were suspected coronary syndrome and myocardial infarction (MI). Control subjects were healthy and had no historic or clinical evidence of coronary artery disease. Enzyme levels were estimated by an Enzyme-linked immunosorbent assay. Patients were seen an average of 4 hours after the onset of chest pain. Plasma myeloperoxidase levels were significantly higher in the study group than in control subjects. They correlated weakly with peak levels of troponin T, C-reactive protein, and age, but not with white cell count. Patients having MI within 16 hours before presentation had especially high myeloperoxidase levels, and the incidence of MI increased with increasing quartiles of myeloperoxidase. Baseline levels were higher in patients who later required revascularization or had a major adverse cardiac event in the next 30 days or 6 months. Multivariate logistic regression analyses confirmed that elevated plasma myeloperoxidase independently predicted an increased risk of MI, the need for revascularization, and major coronary events. Baseline levels helped to identify patients at risk even if troponin T was absent. Plasma myeloperoxidase concentration appears to be a marker of vulnerable coronary artery plaque. It helps to identify patients at risk for major adverse cardiac events independently of evidence that myocardial necrosis is present.
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prognostic value of myeloperoxidase in patients with chest pain
The New England Journal of Medicine, 2003Co-Authors: Marie Luise Brennan, Ronnier J. Aviles, Michael Pepoy, Mehdi H. Shishehbor, Vijay Nambi, Frederick Van Lente, Marc S. Penn, Marlene Goormastic, Ellen McerleanAbstract:background Inflammation is linked to adverse outcomes in acute coronary syndromes. Myeloperoxidase, an abundant Leukocyte Enzyme, is elevated in culprit lesions that have fissured or ruptured in patients with sudden death from cardiac causes. Numerous lines of evidence suggest mechanistic links between myeloperoxidase and both inflammation and cardiovascular disease. methods We assessed the value of plasma levels of myeloperoxidase as a predictor of the risk of cardiovascular events in 604 sequential patients presenting to the emergency department with chest pain. results Initial plasma myeloperoxidase levels predicted the risk of myocardial infarction, even in patients who are negative for troponin T (<0.1 ng per milliliter) at base line (P< 0.001). Myeloperoxidase levels at presentation also predicted the risk of major adverse cardiac events (myocardial infarction, the need for revascularization, or death) within 30 days and 6 months after presentation (P<0.001). In patients without evidence of myocardial necrosis (defined as those who were negative for troponin T), the base-line myeloperoxidase levels independently predicted the risk of major adverse coronary events at 30 days (unadjusted 2nd, 3rd, and 4th quartile odds ratios, 2.2 [95 percent confidence interval, 1.1 to 4.6], 4.2 [95 percent confidence interval, 2.1 to 8.4], and 4.1 [95 percent confidence interval, 2.0 to 8.4], respectively) and at 6 months. conclusions A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain.
A Gorlach - One of the best experts on this subject based on the ideXlab platform.
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Abstract —Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox−/−, and endothelial NO synthase (eNOS)−/− mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS−/− mice, but was attenuated in segments from gp91phox−/− mice. Endothelium-dependent relaxation was greater in aortae from gp91phox−/− than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox−/− mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO. ( Circ Res. 2000;87:26-32.)
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox(-/-), and endothelial NO synthase (eNOS)(-/-) mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS(-/-) mice, but was attenuated in segments from gp91phox(-/-) mice. Endothelium-dependent relaxation was greater in aortae from gp91phox(-/-) than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox(-/-) mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO.
Marie Luise Brennan - One of the best experts on this subject based on the ideXlab platform.
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prognostic value of myeloperoxidase in patients with chest pain
Obstetrical & Gynecological Survey, 2004Co-Authors: Marie Luise Brennan, Ronnier J. Aviles, Michael Pepoy, Mehdi H Shishenbor, Vijay Nambi, Frederick Van Lente, Marc S. Penn, Marlene Goormastic, Ellen McerleanAbstract:The entire process of arterial plaque formation has been linked with inflammation, and extensive infiltration of neutrophils and monocytes is observed in thrombosed plaque in patients with acute coronary disease. One possible means by which Leukocytes could influence the stability of plaque is myeloperoxidase, a Leukocyte Enzyme that is present in elevated amounts in patients with cardiovascular disease. This study examined the possibility that plasma levels of myeloperoxidase might serve as a marker of plaque vulnerability in patients seen in the emergency department with chest pain. The study group included 604 such patients, seen sequentially, whose most frequent final diagnoses were suspected coronary syndrome and myocardial infarction (MI). Control subjects were healthy and had no historic or clinical evidence of coronary artery disease. Enzyme levels were estimated by an Enzyme-linked immunosorbent assay. Patients were seen an average of 4 hours after the onset of chest pain. Plasma myeloperoxidase levels were significantly higher in the study group than in control subjects. They correlated weakly with peak levels of troponin T, C-reactive protein, and age, but not with white cell count. Patients having MI within 16 hours before presentation had especially high myeloperoxidase levels, and the incidence of MI increased with increasing quartiles of myeloperoxidase. Baseline levels were higher in patients who later required revascularization or had a major adverse cardiac event in the next 30 days or 6 months. Multivariate logistic regression analyses confirmed that elevated plasma myeloperoxidase independently predicted an increased risk of MI, the need for revascularization, and major coronary events. Baseline levels helped to identify patients at risk even if troponin T was absent. Plasma myeloperoxidase concentration appears to be a marker of vulnerable coronary artery plaque. It helps to identify patients at risk for major adverse cardiac events independently of evidence that myocardial necrosis is present.
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prognostic value of myeloperoxidase in patients with chest pain
The New England Journal of Medicine, 2003Co-Authors: Marie Luise Brennan, Ronnier J. Aviles, Michael Pepoy, Mehdi H. Shishehbor, Vijay Nambi, Frederick Van Lente, Marc S. Penn, Marlene Goormastic, Ellen McerleanAbstract:background Inflammation is linked to adverse outcomes in acute coronary syndromes. Myeloperoxidase, an abundant Leukocyte Enzyme, is elevated in culprit lesions that have fissured or ruptured in patients with sudden death from cardiac causes. Numerous lines of evidence suggest mechanistic links between myeloperoxidase and both inflammation and cardiovascular disease. methods We assessed the value of plasma levels of myeloperoxidase as a predictor of the risk of cardiovascular events in 604 sequential patients presenting to the emergency department with chest pain. results Initial plasma myeloperoxidase levels predicted the risk of myocardial infarction, even in patients who are negative for troponin T (<0.1 ng per milliliter) at base line (P< 0.001). Myeloperoxidase levels at presentation also predicted the risk of major adverse cardiac events (myocardial infarction, the need for revascularization, or death) within 30 days and 6 months after presentation (P<0.001). In patients without evidence of myocardial necrosis (defined as those who were negative for troponin T), the base-line myeloperoxidase levels independently predicted the risk of major adverse coronary events at 30 days (unadjusted 2nd, 3rd, and 4th quartile odds ratios, 2.2 [95 percent confidence interval, 1.1 to 4.6], 4.2 [95 percent confidence interval, 2.1 to 8.4], and 4.1 [95 percent confidence interval, 2.0 to 8.4], respectively) and at 6 months. conclusions A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain.
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association between myeloperoxidase levels and risk of coronary artery disease
JAMA, 2001Co-Authors: Renliang Zhang, Marie Luise Brennan, Ronnier J. Aviles, Marc S. Penn, Xiaoming Fu, Gregory L Pearce, Eric J Topol, Dennis L Sprecher, Stanley L HazenAbstract:ContextMyeloperoxidase (MPO), a Leukocyte Enzyme that promotes oxidation of lipoproteins in atheroma, has been proposed as a possible mediator of atherosclerosis.ObjectiveTo determine the association between MPO levels and prevalence of coronary artery disease (CAD).Design, Setting, and PatientsCase-control study conducted from July to September 2000 in a US tertiary care referral center, including 158 patients with established CAD (cases) and 175 patients without angiographically significant CAD (controls).Main Outcome MeasuresAssociation of MPO levels per milligram of neutrophil protein (Leukocyte-MPO) and MPO levels per milliliter of blood (blood-MPO) with CAD risk.ResultsLeukocyte- and blood-MPO levels were both significantly greater in patients with CAD than in controls (P<.001). In multivariable models adjusting for traditional cardiovascular risk factors, Framingham risk score, and white blood cell counts, MPO levels were significantly associated with presence of CAD, with an OR of 11.9 (95% CI, 5.5-25.5) for the highest vs lowest quartiles of Leukocyte-MPO and an OR of 20.4 (95% CI, 8.9-47.2) for the highest vs lowest quartiles of blood-MPO.ConclusionsElevated levels of Leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.
M Amidi - One of the best experts on this subject based on the ideXlab platform.
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Abstract —Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox−/−, and endothelial NO synthase (eNOS)−/− mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS−/− mice, but was attenuated in segments from gp91phox−/− mice. Endothelium-dependent relaxation was greater in aortae from gp91phox−/− than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox−/− mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO. ( Circ Res. 2000;87:26-32.)
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a gp91phox containing nadph oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall
Circulation Research, 2000Co-Authors: A Gorlach, Ralf P Brandes, K Nguyen, M Amidi, F Dehghani, Rudi BusseAbstract:Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the Enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the Leukocyte Enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for Leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the Leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox(-/-), and endothelial NO synthase (eNOS)(-/-) mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS(-/-) mice, but was attenuated in segments from gp91phox(-/-) mice. Endothelium-dependent relaxation was greater in aortae from gp91phox(-/-) than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox(-/-) mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing Leukocyte-type NADPH oxidase. This Enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO.