Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF-κB pathway.
Unstable atherosclerotic plaques of the carotid arteries are at great risk for the development of ischemic cerebrovascular events. The degradation of the extracellular matrix by matrix metalloproteinases (MMPs) and NO-induced apoptosis of vascular smooth muscle cells (VSMCs) contribute to the vulnerability of the atherosclerotic plaques. Basic fibroblast growth factor (bFGF) through its mitogenic and angiogenic properties has already been implicated in the pathogenesis of atherosclerosis. However, its role in plaque stability remains elusive. To address this issue, a panel of human carotid atherosclerotic plaques was analyzed for bFGF, FGF-receptors-1 and -2 (FGFR-1/-2), inducible nitric oxide synthase (iNOS) and MMP-9 expression. Our data revealed increased expression of bFGF and FGFR-1 in VSMCs of unstable plaques, implying the existence of an autocrine loop, which significantly correlated with high iNOS and MMP-9 levels. These results were recapitulated in vitro by treatment of VSMCs with bFGF. bFGF administration led to up-regulation of both iNOS and MMP-9 that was specifically mediated by nuclear factor-kappaB (NF-kappaB) activation. Collectively, our data demonstrate a novel NF-kappaB-mediated pathway linking bFGF with iNOS and MMP-9 expression that is associated with carotid plaque vulnerability.
Sigala
Fragiska
F
Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece.
Savvari
Paraskevi
P
Liontos
Michalis
M
Sigalas
Panagiotis
P
Pateras
Ioannis S
IS
Papalampros
Alexandros
A
Basdra
Efthimia K
EK
Kolettas
Evangelos
E
Papavassiliou
Athanasios G
AG
Gorgoulis
Vassilis G
VG
D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D015854:Up-Regulation
D016328:NF-kappa B; D016222:Fibroblast Growth Factor 2; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
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