Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia.
The proteolytic activity of proinflammatory matrix metalloproteinases (MMPs) is elevated in lipid-rich atherosclerotic plaques, thereby contributing to plaque fragility and rupture. We hypothesized that changes in circulating levels of MMPs and their specific inhibitors (TIMPs) could reflect the atherosclerotic process occurring within the arterial wall. We determined serum levels of MMP-3, MMP-9, TIMP-1 and TIMP-2 in dyslipidemic subjects and compared them to those of age- and sex-matched normolipidemic healthy controls. Serum levels of MMP-3, MMP-9 and TIMP-1 were significantly increased in hyperlipidemic subjects versus controls (+54, +29 and +15%, respectively; P<0.001). We also noted a trend to elevated serum MMP-3 levels in patients with atherosclerotic lesions when compared to patients free of atherosclerosis (P=0.07). Circulating levels of MMPs and TIMPs were associated neither with those of C-reactive protein, nor with those of alpha2-macroglobulin (a nonspecific MMP inhibitor), nor with intima-media thickness values. Nonetheless, when divided into tertiles, MMP-3 and TIMP-1 levels in the highest tertile were positively associated with the presence of carotid artery lesions (odds ratios=3.4 and 2.0, confidence intervals 1.7-13.9 and 1.3-7.9, respectively). Thus, serum levels of MMP-3, -9 and TIMP-1 are significantly elevated in asymptomatic hyperlipidemic subjects at high cardiovascular risk; however, MMP-3 and TIMP-1 levels are strongly positively associated with the presence of carotid lesions. Such elevations might reflect enhanced vascular matrix remodeling, a key feature of the progression of atherosclerotic disease.
Beaudeux
Jean-Louis
JL
Department of Clinical Biochemistry, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, Paris Cedex 13 F75651, France. jean-louis.beaudeux@psl.ap-hop-paris.fr
Giral
Philippe
P
Bruckert
Eric
E
Bernard
Marguy
M
Foglietti
Marie-José
MJ
Chapman
M John
MJ
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D000511:alpha-Macroglobulins / Q000032:analysis
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; D019716:Tissue Inhibitor of Metalloproteinase-2; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9