Elevated plasma levels of MMP-12 are associated with atherosclerotic burden and symptomatic cardiovascular disease in subjects with type 2 diabetes

Isabel Goncalves, Eva Bengtsson, Helen M. Colhoun, Angela C. Shore, Carlo Palombo, Andrea Natali, Andreas Edsfeldt, Pontus Dunér, Gunilla Nordin Fredrikson, Harry Björkbacka, Gerd Östling, Kunihiko Aizawa, Francesco Casanova, Margaretha Persson, Kim Gooding, David Strain, Faisel Khan, Helen C. Looker, Fiona Adams, Jill BelchSilvia Pinnoli, Elena Venturi, Michaela Kozakova, Li-Ming Gan, Volker Schnecke, Jan Nilsson

    Research output: Contribution to journalArticle

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    Abstract

    Objective-Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus.

    Approach and Results-Plasma levels of MMP-1, -3, -7, -10, and -12 were analyzed by the Proximity Extension Assay technology in 1500 subjects participating in the SUMMIT (surrogate markers for micro-and macrovascular hard end points for innovative diabetes tools) study, 384 incident coronary cases, and 409 matched controls in the Malmö Diet and Cancer study and in 205 carotid endarterectomy patients. Plasma MMP-7 and -12 were higher in subjects with type 2 diabetes mellitus, increased with age and impaired renal function, and was independently associated with prevalent cardiovascular disease, atherosclerotic burden (as assessed by carotid intima-media thickness and ankle-brachial pressure index), arterial stiffness, and plaque inflammation. Baseline MMP-7 and -12 levels were increased in Malmö Diet and Cancer subjects who had a coronary event during follow-up.

    Conclusions-The plasma level of MMP-7 and -12 are elevated in type 2 diabetes mellitus, associated with more severe atherosclerosis and an increased incidence of coronary events. These observations provide clinical support to previous experimental studies, demonstrating a role for these MMPs in plaque development, and suggest that they are potential biomarkers of atherosclerosis burden and cardiovascular disease risk.

    Original languageEnglish
    Pages (from-to)1723-1731
    Number of pages9
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume35
    Issue number7
    Early online date7 May 2015
    DOIs
    Publication statusPublished - 27 Jul 2015

    Keywords

    • atherosclerosis
    • cardiovascular disease
    • diabetes
    • matrix metalloproteinase

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    Khan, Faisel

    • Systems Medicine - Professor (Teaching and Research) & Professor of Cardiovascular Sciences

    Person: Academic

    Cite this

    Goncalves, I., Bengtsson, E., Colhoun, H. M., Shore, A. C., Palombo, C., Natali, A., Edsfeldt, A., Dunér, P., Fredrikson, G. N., Björkbacka, H., Östling, G., Aizawa, K., Casanova, F., Persson, M., Gooding, K., Strain, D., Khan, F., Looker, H. C., Adams, F., ... Nilsson, J. (2015). Elevated plasma levels of MMP-12 are associated with atherosclerotic burden and symptomatic cardiovascular disease in subjects with type 2 diabetes. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(7), 1723-1731. https://doi.org/10.1161/ATVBAHA.115.305631