Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease

BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as \u3e50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations \u3e322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P \u3c 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27–2.30, P \u3c 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO \u3e322 pmol/L. CONCLUSIONS: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high

Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease

BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as \u3e50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations \u3e322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P \u3c 0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27–2.30, P \u3c 0.001). In patients with increased hsCRP, MPO ≤322 pmol/L was associated with lower event rates than observed with MPO \u3e322 pmol/L. CONCLUSIONS: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high

Complete homochirality induced by the nonlinear autocatalysis and recycling

A nonlinear autocatalysis of a chiral substance is shown to achieve homochirality in a closed system, if the back-reaction is included. Asymmetry in the concentration of two enantiomers or the enantiometric excess increases due to the nonlinear autocatalysis. Furthermore, when the back-reaction is taken into account, the reactant supplied by the decomposition of the enantiomers is recycled to produce more and more the dominant one, and eventually the homochirality is established.Comment: 4 pages, 2 figure

Suite of simple metrics reveals common movement syndromes across vertebrate taxa

ecause empirical studies of animal movement are most-often site- and species-specific, we lack understanding of the level of consistency in movement patterns across diverse taxa, as well as a framework for quantitatively classifying movement patterns. We aim to address this gap by determining the extent to which statistical signatures of animal movement patterns recur across ecological systems. We assessed a suite of movement metrics derived from GPS trajectories of thirteen marine and terrestrial vertebrate species spanning three taxonomic classes, orders of magnitude in body size, and modes of movement (swimming, flying, walking). Using these metrics, we performed a principal components analysis and cluster analysis to determine if individuals organized into statistically distinct clusters. Finally, to identify and interpret commonalities within clusters, we compared them to computer-simulated idealized movement syndromes representing suites of correlated movement traits observed across taxa (migration, nomadism, territoriality, and central place foraging)

EXAFS study of lead-free relaxor ferroelectric BaTi(1-x)Zr(x)O3 at the Zr K-edge

Extended X-ray absorption fine structure (EXAFS) experiments at the Zr K-edge were carried out on perovskite relaxor ferroelectrics BaTi(1-x)Zr(x)O3 (BTZ) (x = 0.25, 0.30, 0.35), and on BaZrO3 for comparison. Structural information up to 4.5 A around the Zr atoms is obtained, revealing that the local structure differs notably from the average Pm-3m cubic structure deduced from X-ray diffraction. In particular, our results show that the distance between Zr atoms and their first oxygen neighbors is independent of the Zr substitution rate x and equal to that measured in BaZrO3, while the X-ray cubic cell parameter increases linearly with x. Furthermore, we show that the Zr atoms tend to segregate in Zr-rich regions. We propose that the relaxor behavior in BTZ is linked to random elastic fields generated by this particular chemical arrangement, rather than to random electric fields as is the case in most relaxors.Comment: 13 pages, 12 figures, 4 tables. Submitted to Phys. Rev.

Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction

Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins

Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction

Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins