Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion
| Autor: | Udo Helmchen, Jürgen Berger, Michelle Ortak, Britta Goldmann, Stephan Baldus, Thomas Heitzer, Bruce A. Freeman, Thomas Meinertz, Thomas Münzel, Denise Lau, Hans-Jürgen Duchstein, Jason P. Eiserich, Susan Petri, Hanke Mollnau |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Neutrophils Myocardial Infarction Myocardial Ischemia Enzyme-Linked Immunosorbent Assay Inflammation Heme Oxidative phosphorylation Nitric Oxide Models Biological Biochemistry Nitric oxide chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Humans Myocardial infarction Endothelial dysfunction Aged Peroxidase biology Catabolism business.industry Myocardium Hydrogen Peroxide Middle Aged medicine.disease Immunohistochemistry Platelet Endothelial Cell Adhesion Molecule-1 Endocrinology chemistry Regional Blood Flow Case-Control Studies Reperfusion Injury Myeloperoxidase Reperfusion biology.protein Cardiology Female Rabbits medicine.symptom business Reperfusion injury |
| Zdroj: | Free Radical Biology and Medicine. 37:902-911 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2004.06.003 |
| Popis: | Impaired microvascular function during myocardial ischemia and reperfusion is associated with recruitment of polymorphonuclear neutrophils (PMN) and has been attributed to decreased bioavailability of nitric oxide (NO). Whereas myeloperoxidase (MPO), a highly abundant, PMN-derived heme protein facilitates oxidative NO consumption and impairs vascular function in animal models of acute inflammation, its capacity to function in this regard during human myocardial ischemia and reperfusion remains unknown. Plasma samples from 30 consecutive patients (61 +/- 14 years, 80% male) presenting with acute myocardial infarction were collected 9 +/- 4 h after vessel recanalization and compared to plasma from healthy control subjects (n = 12). Plasma levels of MPO were higher in patients than in control subjects (1.4 +/- 0.9 vs 0.3 +/- 0.2 ng/mg protein, respectively, p0.0001). The addition of hydrogen peroxide to patient plasma resulted in accelerated rates of NO consumption compared to control subjects (0.53 +/- 0.25 vs 0.068 +/- 0.039 nM/s/mg protein, respectively, p0.0001). Myocardial tissue from patients with the same pathology revealed intense recruitment of MPO-positive PMN localized along infarct-related vessels as well as diffuse endothelial distribution of non-PMN-associated MPO immunoreactivity. Endothelium-dependent microvascular function, as assessed by an acetylcholine-dependent increase in forearm blood flow in 75 patients with symptomatic coronary artery disease, inversely correlated with MPO plasma levels (r = -0.75, p0.005). Plasma from patients undergoing myocardial reperfusion contained increased levels of MPO, which catalytically consumed NO in the presence of H(2)O(2). Given the correlation between intravascular MPO levels and forearm vasomotor function in patients with coronary artery disease, MPO appears to be an important modulator of vasomotor function in inflammatory vascular disease and a potential therapeutic target for treatment. |
| Databáze: | OpenAIRE |
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