Open AccessIncreased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF‐κB pathway
Author(s) -
Sigala Fragiska,
Savvari Paraskevi,
Liontos Michalis,
Sigalas Panagiotis,
Pateras Ioannis S.,
Papalampros Alexandros,
Basdra Efthimia K.,
Kolettas Evangelos,
Kotsinas Athanassios,
Papavassiliou Athanasios G.,
Gorgoulis Vassilis G.
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01082.x
Subject(s) - basic fibroblast growth factor , autocrine signalling , matrix metalloproteinase , nitric oxide synthase , vascular smooth muscle , nitric oxide , extracellular matrix , signal transduction , microbiology and biotechnology , fibroblast growth factor , medicine , cancer research , endocrinology , biology , receptor , growth factor , smooth muscle
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 nitric oxide 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 analysed 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‐κB (NF‐κB) activation. Collectively, our data demonstrate a novel NF‐κB‐mediated pathway linking bFGF with iNOS and MMP‐9 expression that is associated with carotid plaque vulnerability.