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Biomarkers of Extracellular Matrix Metabolism (MMP-9 and TIMP-1) and Risk of Stroke, Myocardial Infarction, and Cause-Specific Mortality: Cohort Study
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
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2011 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 6, nr 1, s. e16185-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.

Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991-1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).

Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03-1.19; and 1.11, 1.02-1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09-1.37; and 1.18, 1.04-1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.

Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

Ort, förlag, år, upplaga, sidor
2011. Vol. 6, nr 1, s. e16185-
Nationell ämneskategori
Medicin och hälsovetenskap Kirurgi
Forskningsämne
Ortopedi
Identifikatorer
URN: urn:nbn:se:uu:diva-146287DOI: 10.1371/journal.pone.0016185ISI: 000286520600027PubMedID: 21283828OAI: oai:DiVA.org:uu-146287DiVA, id: diva2:397931
Tillgänglig från: 2011-02-16 Skapad: 2011-02-16 Senast uppdaterad: 2018-11-30

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Larsson, AndersMichaëlsson, Karl
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MedicinGeriatrikInstitutionen för medicinska vetenskaperKlinisk kemiInstitutionen för kirurgiska vetenskaperUppsala kliniska forskningscentrum (UCR)
Medicin och hälsovetenskapKirurgi

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