Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation.

Abstract

OBJECTIVES:

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.

• Authors: Camilla Smith, Jan K Damås, Kari Otterdal, Erik Øie, Wiggo J Sandberg, Arne Yndestad, Torgun Waehre, Hanne Scholz, Knut Endresen, Peder S Olofsson, Bente Halvorsen, Lars Gullestad, Stig S Frøland, Gøran K Hansson, Pål Aukrust
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 48 Issue 8 Pg. 1591-9 (Oct 17 2006) ISSN: 1558-3597 [Electronic] United States
• PMID: 17045893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• Chemokines
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• PPBP protein, human
• Receptors, Peptide
• Recombinant Proteins
• beta-Thromboglobulin
• neutrophil-activating peptide 2 receptor, human
• Aspirin

Topics

• Acute Disease
• Angina Pectoris (blood)
• Angina, Unstable (blood)
• Arteries
• Aspirin (pharmacology)
• Blood Platelets (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cells, Cultured
• Chemokines (metabolism)
• Chemotaxis (drug effects)
• Coronary Disease (blood)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Intracranial Arteriosclerosis (metabolism, pathology)
• Macrophages (metabolism)
• Monocytes (drug effects, metabolism)
• Muscle, Smooth, Vascular (metabolism, pathology)
• Myocytes, Smooth Muscle (metabolism)
• Platelet Count
• Receptors, Peptide (blood, metabolism)
• Recombinant Proteins (pharmacology)
• Syndrome
• T-Lymphocytes (metabolism)
• Thrombosis (blood)
• Vasculitis (etiology)
• beta-Thromboglobulin (metabolism, pharmacology)