TY - JOUR
T1 - Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion
AU - Baldus, Stephan
AU - Heitzer, Thomas
AU - Eiserich, Jason P.
AU - Lau, Denise
AU - Mollnau, Hanke
AU - Ortak, Michelle
AU - Petri, Susan
AU - Goldmann, Britta
AU - Duchstein, Hans Jürgen
AU - Berger, Jürgen
AU - Helmchen, Udo
AU - Freeman, Bruce A.
AU - Meinertz, Thomas
AU - Münzel, Thomas
PY - 2004/9/15
Y1 - 2004/9/15
N2 - 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.
AB - 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.
KW - Endothelial dysfunction
KW - Free radicals
KW - Hydrogen peroxide
KW - Myeloperoxidase
KW - Myocardial infarction
KW - Nitric oxide
KW - Polymorphonuclear neutrophils
KW - Reperfusion
UR - http://www.scopus.com/inward/record.url?scp=4043072706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4043072706&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2004.06.003
DO - 10.1016/j.freeradbiomed.2004.06.003
M3 - Article
C2 - 15304260
AN - SCOPUS:4043072706
VL - 37
SP - 902
EP - 911
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 6
ER -