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Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia.
Atherosclerosis. 2003 Jul; 169(1):139-46.A

Abstract

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.

Authors+Show Affiliations

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.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12860260

Citation

Beaudeux, Jean-Louis, et al. "Serum Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinases-1 as Potential Markers of Carotid Atherosclerosis in Infraclinical Hyperlipidemia." Atherosclerosis, vol. 169, no. 1, 2003, pp. 139-46.
Beaudeux JL, Giral P, Bruckert E, et al. Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia. Atherosclerosis. 2003;169(1):139-46.
Beaudeux, J. L., Giral, P., Bruckert, E., Bernard, M., Foglietti, M. J., & Chapman, M. J. (2003). Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia. Atherosclerosis, 169(1), 139-46.
Beaudeux JL, et al. Serum Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinases-1 as Potential Markers of Carotid Atherosclerosis in Infraclinical Hyperlipidemia. Atherosclerosis. 2003;169(1):139-46. PubMed PMID: 12860260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia. AU - Beaudeux,Jean-Louis, AU - Giral,Philippe, AU - Bruckert,Eric, AU - Bernard,Marguy, AU - Foglietti,Marie-José, AU - Chapman,M John, PY - 2003/7/16/pubmed PY - 2003/12/5/medline PY - 2003/7/16/entrez SP - 139 EP - 46 JF - Atherosclerosis JO - Atherosclerosis VL - 169 IS - 1 N2 - 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. SN - 0021-9150 UR - https://www.unboundmedicine.com/medline/citation/12860260/Serum_matrix_metalloproteinase_3_and_tissue_inhibitor_of_metalloproteinases_1_as_potential_markers_of_carotid_atherosclerosis_in_infraclinical_hyperlipidemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(03)00149-7 DB - PRIME DP - Unbound Medicine ER -