Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET)

Eur J Vasc Endovasc Surg. 2009 Jun;37(6):714-21. doi: 10.1016/j.ejvs.2008.11.018. Epub 2008 Dec 27.

Abstract

Objectives: Atherosclerosis is recognised as an inflammatory disease, and new diagnostic tools are warranted to evaluate plaque inflammatory activity and risk of cardiovascular events. We investigated [18]-fluorodeoxyglucose (FDG) uptake in vulnerable carotid plaques visualised by positron emission tomography (PET). Uptake was correlated to quantitative gene expression of known markers of inflammation and plaque vulnerability.

Methods: Ten patients with recent transient ischaemic attack and carotid artery stenosis (>50%) underwent combined FDG-PET and computed tomography angiography (CTA) the day before carotid endarterectomy. Plaque mRNA expression of the inflammatory cytokine interleukin 18 (IL-18), the macrophage-specific marker CD68 and the two proteinases, Cathepsin K and matrix metalloproteinase 9 (MMP-9), were quantified using real-time quantitative polymerase chain reaction.

Results: Consistent up-regulation of CD68 (3.8-fold+/-0.9; mean+/-standard error), Cathepsin K (2.1-fold+/-0.5), MMP-9 (122-fold+/-65) and IL-18 (3.4-fold+/-0.7) were found in the plaques, compared to reference-artery specimens. The FDG uptake by plaques was strongly correlated with CD68 gene expression (r=0.71, P=0.02). Any correlations with Cathepsin K, MMP-9 or IL-18 gene expression were weaker.

Conclusions: FDG-PET uptake in carotid plaques is correlated to gene expression of CD68 and other molecular markers of inflammation and vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Carotid Stenosis / complications
  • Carotid Stenosis / diagnostic imaging*
  • Carotid Stenosis / genetics
  • Carotid Stenosis / surgery
  • Cathepsin K
  • Cathepsins / genetics
  • Endarterectomy, Carotid
  • Female
  • Fluorodeoxyglucose F18*
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / analysis
  • Interleukin-18 / genetics
  • Ischemic Attack, Transient / diagnostic imaging
  • Ischemic Attack, Transient / etiology*
  • Ischemic Attack, Transient / genetics
  • Ischemic Attack, Transient / surgery
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • Radiopharmaceuticals*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Severity of Illness Index
  • Tomography, X-Ray Computed

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Inflammation Mediators
  • Interleukin-18
  • RNA, Messenger
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K
  • Matrix Metalloproteinase 9