Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

Nicholls, Stephen J.; Tang, W.H. Wilson; Brennan, Danielle M.; Brennan, Marie Luise; Mann, Shirley; Nissen, Steven E.; Hazen, Stanley L.

doi:10.1373/clinchem.2011.166827

Cited by 39 publications

(33 citation statements)

References 39 publications

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“…Previous studies have provided compelling evidence for an association between elevated levels of MPO and increased atherosclerosis and cardiovascular disease [30,31]. However, the nature of the oxidants that gives rise to this elevated risk remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

Morgan

Laurà

Maki

et al. 2015

Free Radical Research

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Elevated levels of the heme enzyme myeloperoxidase (MPO) are associated with adverse cardiovascular outcomes. MPO predominantly catalyzes formation of the oxidants hypochlorous acid (HOCl) from Cl−, and hypothiocyanous acid (HOSCN) from SCN−, with these anions acting as competitive substrates. HOSCN is a less powerful and more specific oxidant than HOCl, and selectively targets thiols; such damage is largely reversible, unlike much HOCl-induced damage. We hypothesized that increased plasma SCN−, and hence HOSCN formation instead of HOCl, may decrease artery wall damage. This was examined using high-fat fed atherosclerosis-prone LDLR−/− mice transgenic for human MPO, with and without SCN− (10 mM) added to drinking water. Serum samples, collected fortnightly, were analyzed for cholesterol, triglycerides, thiols, MPO and SCN−; study-long exposure was calculated by area under the curve (AUC). Mean serum SCN− concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (<120 μM). Normalized aortic root plaque areas at sacrifice were 26% lower in the SCN−-supplemented mice compared to controls (P=0.0417), but plaque morphology was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN−- supplemented vs. control mice showed no significant changes in MPO protein, cholesterol or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque areas increased with higher cholesterol AUC (r=0.4742; P=0.0468), and decreased with increasing SCN− AUC (r=−0.5693; P=0.0134). These data suggest that increased serum SCN− levels, which can be achieved in humans by dietary manipulation, may decrease atherosclerosis burden.

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Section: Discussionmentioning

confidence: 99%

Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

Morgan

Laurà

Maki

et al. 2015

Free Radical Research

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“…Serial measurements are predictive of acute progression from ACS to a MACE in patients with negative troponin I levels24. It has also been shown to predict CVD development in otherwise healthy individuals25.…”

Section: Discussionmentioning

confidence: 99%

A rapid bioluminescence assay for measuring myeloperoxidase activity in human plasma

2015

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Myeloperoxidase (MPO) is a circulating cardiovascular disease (CVD) biomarker used to estimate clinical risk and patient prognosis. Current enzyme-linked immunosorbent assays (ELISA) for MPO concentration are costly and time-intensive. Here we report a novel bioluminescence assay, designated MPO activity on a polymer surface (MAPS), for measuring MPO activity in human plasma samples using the bioluminescent substrate L-012. The method delivers a result in under an hour and is resistant to confounding effects from endogenous MPO inhibitors. In a pilot clinical study, we compared MAPS and two clinical ELISAs using 72 plasma samples from cardiac catheterization patients. Results from parallel MAPS and ELISAs were concordant within 2±11 μg l−1 MPO with similar uncertainty and reproducibility. Results between parallel MAPS and ELISA were in better agreement than those between independent ELISAs. MAPS may provide an inexpensive and rapid assay for determining MPO activity in plasma samples from patients with CVD or potentially other immune and inflammatory disorders.

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“…A, B, and C represent control group, model group, and PNS group, respectively substances to promote development of atherosclerotic plaque. It can further cause several complications such as acute coronary syndrome and is closely related to cancer [30]. One research reported that when ICAM-1 expression on tissue surface increased, a large amount of PMNLs remained on pulmonary capillaries and tissue space by the interaction between ICAM-1 and CD11b/CD18, which may cause acute inflammatory injury.…”

Section: Discussionmentioning

confidence: 99%

Protective Mechanism of Panax notoginseng Saponins on Rat Hemorrhagic Shock Model in Recovery Stage

Liu

Zhao

et al. 2014

Cell Biochem Biophys

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To explore protective mechanism of Panax notoginseng saponins (PNS) on rat hemorrhagic shock model in recovery stage. 72 Wistar rats were selected and divided into control group, model group and PNS group with 24 rats in each group. 200 mg/kg PNS was injected intravenously at 60 min of hemorrhagic shock stage in PNS groups. Changes of endotoxin, MPO, IL-6, SOD, MDA and TNF α were observed at 30 and 120 min of recovery stage by ELISA; water content of lung and intestine was detected; HE staining was applied to observe morphological change of intestinal mucosa, kidney, liver and lung; western blot was used to detect intercellular adhesion molecule-1 (ICAM-1) level in lung tissue and intestine tissue. At 30 min and 120 min of recovery stage, MDA, MPO, endotoxin, TNF α and IL-6 levels significantly increased in model group compared with control group, however SOD level significantly decreased, the difference was statistically significant (P < 0.05); PNS dose-dependently decreased MDA, MPO, endotoxin, TNF α and IL-6 levels, and increased SOD level, which was statistically significant (P < 0.05); In results of water content detection, water content in lung tissue and intestine tissue was significantly higher than in control group, however, after being treated with PNS, the water content was significantly decreased; HE staining showed the morphologic change of lung tissue cells; Western blot showed that in lung tissue and intestine tissue, ICAM-1 level in model group was significantly higher than in control group, and it was lower in PNS group than in model group. PNS can increase SOD activity, decrease levels of MDA, endotoxin and MPO, decrease expression of TNF α and IL-6, and decrease water content in lung tissue and intestine tissue. Thus, PNS is protective to rat hemorrhagic shock model by anti oxidative stress and anti-inflammatory pathways, and ICAM-1 may play an important role in the mechanism.

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Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

Cited by 39 publications

References 39 publications

Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

A rapid bioluminescence assay for measuring myeloperoxidase activity in human plasma

Protective Mechanism of Panax notoginseng Saponins on Rat Hemorrhagic Shock Model in Recovery Stage

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