Inflammatory markers at the site of ruptured plaque in acute myocardial infarction: locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein

Circulation. 2005 Mar 22;111(11):1355-61. doi: 10.1161/01.CIR.0000158479.58589.0A. Epub 2005 Mar 7.

Abstract

Background: Acute myocardial infarction (AMI) is associated with inflammation. However, it remains unclear whether it originates from the ruptured plaque or represents a systemic process.

Methods and results: In 42 patients with AMI, a balloon-based embolization protection device and aspiration catheter (PercuSurge) were used during acute coronary interventions. Samples from the site of the ruptured plaque were taken under distal balloon occlusion. Systemic samples were taken from the aorta. Sera, plaques, and thrombi were analyzed for inflammatory markers and lipoproteins. Systemic levels of C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA) in the aorta amounted to 3.0 mg/L, 5.0 ng/L, and 22.1 mg/L, respectively (interquartile ranges [IQRs], 1.1 to 7.4 mg/L, 5.0 to 6.5 ng/L, and 13.9 to 27.0 mg/L, respectively). In blood surrounding ruptured plaques, local levels of IL-6 (8.9 ng/L; IQR, 5.0 to 16.9 ng/L) and SAA (24.3 mg/L; IQR, 16.3 to 44.0 mg/L) were significantly higher, whereas CRP levels (2.5 mg/L; IQR, 0.9 to 7.7 mg/L) were decreased compared with the aorta (all P<0.0001). The coronary levels of IL-6 determined in vivo showed biological activity in vitro. Harvested thrombus contained CD68-positive monocytes expressing IL-6 and showed extracellularly and intracellularly positive staining for SAA, whereas CRP was found exclusively in the cytoplasm of phagocyting white blood cells.

Conclusions: Coronary levels of IL-6 and SAA at the site of plaque rupture were increased relative to the systemic circulation, indicating local production of biologically active inflammatory mediators. In contrast, CRP was locally decreased, at least in part by uptake by the phagocyting cells, suggesting a systemic origin of the protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary
  • Aorta / chemistry
  • Arteriosclerosis / metabolism*
  • Biomarkers
  • C-Reactive Protein / analysis*
  • Coronary Thrombosis / metabolism
  • Coronary Vessels / chemistry
  • Female
  • Humans
  • Inflammation Mediators / analysis*
  • Interleukin-6 / analysis*
  • Interleukin-6 / blood
  • Lipoproteins / analysis
  • Male
  • Middle Aged
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / therapy
  • Organ Specificity
  • Rupture, Spontaneous
  • Serum Amyloid A Protein / analysis*

Substances

  • Biomarkers
  • Inflammation Mediators
  • Interleukin-6
  • Lipoproteins
  • Serum Amyloid A Protein
  • C-Reactive Protein