Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion

Stephan Baldus, Thomas Heitzer, Jason P. Eiserich, Denise Lau, Hanke Mollnau, Michelle Ortak, Susan Petri, Britta Goldmann, Hans Jürgen Duchstein, Jürgen Berger, Udo Helmchen, Bruce A. Freeman, Thomas Meinertz, Thomas Münzel

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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, p < 0.0001). 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, p < 0.0001). 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, p < 0.005). Plasma from patients undergoing myocardial reperfusion contained increased levels of MPO, which catalytically consumed NO in the presence of H 2O 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.

Original languageEnglish (US)
Pages (from-to)902-911
Number of pages10
JournalFree Radical Biology and Medicine
Volume37
Issue number6
DOIs
StatePublished - Sep 15 2004

Fingerprint

Myocardial Reperfusion
Peroxidase
Myocardial Ischemia
Nitric Oxide
Plasmas
Neutrophils
Forearm
Coronary Artery Disease
Hemeproteins
Neutrophil Infiltration
Pathology
Vascular Diseases
Hydrogen Peroxide
Modulators
Biological Availability
Acetylcholine
Endothelium
Blood Vessels
Healthy Volunteers
Animals

Keywords

  • Endothelial dysfunction
  • Free radicals
  • Hydrogen peroxide
  • Myeloperoxidase
  • Myocardial infarction
  • Nitric oxide
  • Polymorphonuclear neutrophils
  • Reperfusion

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Baldus, S., Heitzer, T., Eiserich, J. P., Lau, D., Mollnau, H., Ortak, M., ... Münzel, T. (2004). Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. Free Radical Biology and Medicine, 37(6), 902-911. https://doi.org/10.1016/j.freeradbiomed.2004.06.003

Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. / Baldus, Stephan; Heitzer, Thomas; Eiserich, Jason P.; Lau, Denise; Mollnau, Hanke; Ortak, Michelle; Petri, Susan; Goldmann, Britta; Duchstein, Hans Jürgen; Berger, Jürgen; Helmchen, Udo; Freeman, Bruce A.; Meinertz, Thomas; Münzel, Thomas.

In: Free Radical Biology and Medicine, Vol. 37, No. 6, 15.09.2004, p. 902-911.

Research output: Contribution to journalArticle

Baldus, S, Heitzer, T, Eiserich, JP, Lau, D, Mollnau, H, Ortak, M, Petri, S, Goldmann, B, Duchstein, HJ, Berger, J, Helmchen, U, Freeman, BA, Meinertz, T & Münzel, T 2004, 'Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion', Free Radical Biology and Medicine, vol. 37, no. 6, pp. 902-911. https://doi.org/10.1016/j.freeradbiomed.2004.06.003
Baldus, Stephan ; Heitzer, Thomas ; Eiserich, Jason P. ; Lau, Denise ; Mollnau, Hanke ; Ortak, Michelle ; Petri, Susan ; Goldmann, Britta ; Duchstein, Hans Jürgen ; Berger, Jürgen ; Helmchen, Udo ; Freeman, Bruce A. ; Meinertz, Thomas ; Münzel, Thomas. / Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. In: Free Radical Biology and Medicine. 2004 ; Vol. 37, No. 6. pp. 902-911.
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