TY - JOUR

T1 - Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET)

AU - Graebe, M

AU - Pedersen, Sune Folke

AU - Borgwardt, L

AU - Højgaard, L

AU - Sillesen, H

AU - Kjær, Andreas

N1 - Keywords: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carotid Stenosis; Cathepsin K; Cathepsins; Endarterectomy, Carotid; Female; Fluorodeoxyglucose F18; Gene Expression Regulation; Humans; Inflammation Mediators; Interleukin-18; Ischemic Attack, Transient; Male; Matrix Metalloproteinase 9; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; RNA, Messenger; Radiopharmaceuticals; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Severity of Illness Index; Tomography, X-Ray Computed

PY - 2008

Y1 - 2008

N2 - 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 Udgivelsesdato: 2009/6

AB - 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 Udgivelsesdato: 2009/6

U2 - 10.1016/j.ejvs.2008.11.018

DO - 10.1016/j.ejvs.2008.11.018

M3 - Journal article

C2 - 19112034

VL - 37

SP - 714

EP - 721

JO - European Journal of Vascular and Endovascular Surgery

JF - European Journal of Vascular and Endovascular Surgery

SN - 1078-5884

IS - 6

ER -