Coronary plaque injury triggers neutrophil activation in patients with coronary artery disease.
Activation of leukocytes, in particular polymorphonuclear neutrophils (PMN), is considered an early event in unstable coronary disease. Upon activation PMN liberate myeloperoxidase (MPO), an enzyme which binds to the vessel wall and depletes vascular NO bioavailability. Using coronary balloon angioplasty as a trigger to provoke coronary plaque injury, we assessed the time course of neutrophil activation, local and peripheral levels of myeloperoxidase, and systemic vascular NO bioavailability in patients with stable coronary artery disease. Twenty-four patients with stable CAD were enrolled prior to undergoing percutaneous interventions (PCI, n=14) and diagnostic coronary angiography (n=10), respectively. Following angioplasty arterial MPO plasma levels increased (231.5+/-67.6 to 273.8+/-80.4 pg/mg protein; P<0.01) whereas MPO levels in the coronary sinus decreased (240.8+/-74.4 vs 205.4+/-60.1 pg/mg protein; P<0.01) in the absence of elevated serum markers for myocardial necrosis. Following PCI, patients revealed impaired vascular NO bioavailability as reflected by reduced brachial flow-mediated dilation (FMD; 6.25+/-3.03 to 4.90+/-2.70%; P<0.01), whereas FMD increased in the angiography group. Coronary plaque injury provokes rapid activation of PMN in the absence of myocardial necrosis; the coronary circulation emerges as a primary site for deposition of MPO following injury of the coronary vessel wall. Activation of PMN with release of MPO is not only restricted to the target site, but can be assessed systemically and may represent a critical mechanistic link for impaired systemic vascular NO bioavailability in patients suffering unstable coronary disease.
Rudolph
Volker
V
Department of Cardiology, Heart Center, University Hospital Hamburg Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Steven
Daniel
D
Gehling
Ursula M
UM
Goldmann
Britta
B
Rudolph
Tanja K
TK
Friedrichs
Kai
K
Meinertz
Thomas
T
Heitzer
Thomas
T
Baldus
Stephan
S
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D018375:Neutrophil Activation; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000097:blood
D015415:Biomarkers; D009569:Nitric Oxide; D009195:Peroxidase