Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation.
OBJECTIVE
We sought to investigate the role of the CXC chemokine neutrophil-activating peptide-2 (NAP-2) in atherogenesis and plaque destabilization.


BACKGROUND
Chemokines are involved in atherogenesis, but the role of NAP-2 in atherosclerotic disorders is unclear. Based on its potential pro-atherogenic properties, we hypothesized a pathogenic role for NAP-2 in coronary artery disease.


METHODS
We tested this hypothesis by differential experimental approaches including studies in patients with stable (n = 40) and unstable angina (n = 40) and healthy control subjects (n = 20).


RESULTS
The following results were discovered: 1) patients with stable, and particularly those with unstable, angina had markedly raised plasma levels of NAP-2 compared with control subjects, accompanied by increased expression of CXC receptor 2 in monocytes; 2) platelets, but also peripheral blood mononuclear cells (PBMCs), released large amounts of NAP-2 upon stimulation, with a particularly prominent PBMC response in unstable angina; 3) NAP-2 protein was detected in macrophages and smooth muscle cells of atherosclerotic plaques and in monocytes and platelets of coronary thrombi; 4) in vitro, recombinant and platelet-derived NAP-2 increased the expression of adhesion molecules and chemokines in endothelial cells; and 5) whereas aspirin reduced plasma levels of NAP-2, statin therapy increased NAP-2 with stimulating effects both on platelets and leukocytes.


CONCLUSIONS
Our findings suggest that NAP-2 has the potential to induce inflammatory responses within the atherosclerotic plaque. By its ability to promote leukocyte and endothelial cell activation, such a NAP-2-driven inflammation could promote plaque rupture and acute coronary syndromes.
Smith
Camilla
C
Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway.
Damås
Jan K
JK
Otterdal
Kari
K
Øie
Erik
E
Sandberg
Wiggo J
WJ
Yndestad
Arne
A
Waehre
Torgun
T
Scholz
Hanne
H
Endresen
Knut
K
Olofsson
Peder S
PS
Halvorsen
Bente
B
Gullestad
Lars
L
Frøland
Stig S
SS
Hansson
Gøran K
GK
Aukrust
Pål
P
D000208:Acute Disease; D000787:Angina Pectoris / Q000097:blood; D000789:Angina, Unstable / Q000097:blood; D001158:Arteries; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D002537:Intracranial Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010976:Platelet Count; D018000:Receptors, Peptide / Q000097:blood / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism; D013927:Thrombosis / Q000097:blood; D014657:Vasculitis / Q000209:etiology; D001620:beta-Thromboglobulin / Q000378:metabolism* / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D018925:Chemokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C061615:PPBP protein, human; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D001620:beta-Thromboglobulin; C514928:neutrophil-activating peptide 2 receptor, human; D001241:Aspirin