Myeloperoxidase-Generated Oxidants Modulate Left Ventricular Remodeling but Not Infarct Size After Myocardial Infarction
- 1 November 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 112 (18), 2812-2820
- https://doi.org/10.1161/circulationaha.105.542340
Abstract
Background— Inflammation after myocardial infarction (MI) heralds worse left ventricular (LV) function and clinical outcomes. However, whether inflammation affects LV function by extending myonecrosis and/or altering LV remodeling remains unknown. We hypothesized that cytotoxic aldehydes generated during oxidative stress may adversely affect remodeling and infarct size. One theoretical source of reactive aldehydes is oxidation of common α-amino acids by myeloperoxidase (MPO) released by leukocytes. However, a role for MPO in formation of aldehydes in vivo and the functional consequences of MPO-generated oxidants in ischemia/reperfusion models of MI have not been established. Methods and Results— In studies with cell types found in vascular tissue, MPO-oxidation products of glycine (formaldehyde) and threonine (acrolein) were the most cytotoxic. Mass spectrometry studies of myocardial tissue from murine models of acute MI (both chronic left anterior descending coronary artery ligation and ischemia/reperfusion injury) confirmed that MPO serves as a major enzymatic source in the generation of these cytotoxic aldehydes. Interestingly, although MPO-null mice experienced 35.1% ( P P Conclusions— The present data separate inflammatory effects on infarct size and LV remodeling and demonstrate that MPO-generated oxidants do not significantly affect tissue necrosis after MI but rather have a profound adverse effect on LV remodeling and function.This publication has 29 references indexed in Scilit:
- Myeloperoxidase and Plaque VulnerabilityArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- Myeloperoxidase and Plasminogen Activator Inhibitor 1 Play a Central Role in Ventricular Remodeling after Myocardial InfarctionThe Journal of Experimental Medicine, 2003
- Hypochlorous Acid Oxygenates the Cysteine Switch Domain of Pro-matrilysin (MMP-7)Online Journal of Public Health Informatics, 2001
- Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarctionJCI Insight, 2000
- p-Hydroxyphenylacetaldehyde, the Major Product of l-Tyrosine Oxidation by the Myeloperoxidase-H2O2-Chloride System of Phagocytes, Covalently Modifies ε-Amino Groups of Protein Lysine ResiduesOnline Journal of Public Health Informatics, 1997
- p-Hydroxyphenylacetaldehyde Is the Major Product of L-Tyrosine Oxidation by Activated Human PhagocytesOnline Journal of Public Health Informatics, 1996
- Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenalFree Radical Biology & Medicine, 1991
- Rat glutathione transferase 8‐8, an enzyme efficiently detoxifying 4‐hydroxyalk‐2‐enalsFEBS Letters, 1986
- Oxygen-Dependent Microbial Killing by PhagocytesThe New England Journal of Medicine, 1978
- Myeloperoxidase of Human Leukaemic LeucocytesEuropean Journal of Biochemistry, 1968