Basic fibroblast growth factor mediates carotid plaque instability through metalloproteinase-2 and -9 expression.
OBJECTIVE
We hypothesized that basic fibroblast growth factor (bFGF) may exert a role in carotid plaque instability by regulating the expression of matrix metalloproteinases (MMP).


METHODS
Plaques obtained from 40 consecutive patients undergoing carotid endarterectomy were preoperatively classified as soft or hard. Serum bFGF was pre- and postoperatively measured. The release of MMP-2 and MMP-9 in the blood serum, and the activity, production and expression in the carotid specimens was analyzed. Specific anti-bFGF inhibition tests were performed in vitro on human umbilical artery smooth muscle cells (HUASMC) to evaluate the role of bFGF in the activity, production and expression of MMP-2 and -9.


RESULTS
Twenty-one (53%) patients had a soft carotid plaque and 19 (48%) a hard plaque. Preoperative bFGF serum levels were higher in patients with soft plaques [soft=34 (28-39) pg/mL and hard=20 (17-22) pg/mL-p<0.001] and postoperatively returned to normal values (when compared to 10 healthy volunteers). The serum levels of MMP-2 in patients' with soft plaques were higher than those in patients' with hard plaques [soft=1222 (1190-1252) ng/mL and hard=748 (656-793)ng/mL-p<0.0001]. MMP-9 serum values were 26 (22-29) ng/mL for soft plaques and 18 (15-21) ng/mL for hard plaques (p<0.0001). We found increased activity, production and expression of MMP-2 and -9 in soft plaques compared to hard plaques (p<0.001). In vitro inhibition tests on HUASMC showed the direct influence of bFGF on the activity, production and expression of MMP-2 and -9 (p<0.001).


CONCLUSIONS
bFGF seems to exert a key role in carotid plaque instability regulating the activity, production and expression of MMP thus altering the physiologic homeostasis of the carotid plaque.
Sapienza
P
P
Department of Surgery 'Pietro Valdoni', University of Rome 'La Sapienza', Rome, Italy.
di Marzo
L
L
Borrelli
V
V
Sterpetti
A V
AV
Mingoli
A
A
Piagnerelli
R
R
Cavallaro
A
A
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002343:Carotid Artery, Internal / Q000378:metabolism* / Q000473:pathology*; D016893:Carotid Stenosis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014469:Umbilical Arteries / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9