Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET).
OBJECTIVE
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.
Graebe
M
M
Department of Vascular Surgery, Rigshospitalet RK-3111, University of Copenhagen, Copenhagen E, Denmark. martin.graebe@rh.regionh.dk
Pedersen
S F
SF
Borgwardt
L
L
Højgaard
L
L
Sillesen
H
H
Kjaer
A
A
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D016893:Carotid Stenosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics / Q000601:surgery; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D016894:Endarterectomy, Carotid; D005260:Female; D019788:Fluorodeoxyglucose F18; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D020382:Interleukin-18 / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000601:surgery; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D019275:Radiopharmaceuticals; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D056657:Cathepsin K; D002403:Cathepsins; D019788:Fluorodeoxyglucose F18; D018836:Inflammation Mediators; D020382:Interleukin-18; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C534130:CTSK protein, human