S A Peeters1, L Engelen2, J Buijs3, S Theilade4, P Rossing5, C G Schalkwijk6, C D A Stehouwer7. 1. Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands. Electronic address: stijn.peeters@mumc.nl. 2. Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Centraal Bureau voor de Statistiek, Heerlen, The Netherlands. 3. Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands. Electronic address: j.buijs@zuyderland.nl. 4. Steno Diabetes Center Copenhagen, Gentofte, Denmark. Electronic address: karen.simone.theilade.01@regionh.dk. 5. Steno Diabetes Center Copenhagen, Gentofte, Denmark; University of Copenhagen, Copenhagen, Denmark. Electronic address: peter.rossing@regionh.dk. 6. Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: c.schalkwijk@maastrichtuniversity.nl. 7. Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: cda.stehouwer@mumc.nl.
Abstract
AIMS: Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes. METHODS: In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes, and additionally for other potential confounders and presence of vascular complication. RESULTS: After full adjustment, levels of CML were positively associated with levels of MMP-2 and inversely with MMP-9. CEL was positively associated with MMP-3 and TIMP-1. MG-H1 was only associated with TIMP-1, whereas pentosidine was not associated with MMPs or TIMP-1. CONCLUSIONS: We showed independent associations between several AGEs and markers of the MMP-TIMP system, which indicate specific AGE-MMP/TIMP-1 interactions potentially contributing to vascular complications in patients with type 1 diabetes.
AIMS: Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes. METHODS: In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes, and additionally for other potential confounders and presence of vascular complication. RESULTS: After full adjustment, levels of CML were positively associated with levels of MMP-2 and inversely with MMP-9. CEL was positively associated with MMP-3 and TIMP-1. MG-H1 was only associated with TIMP-1, whereas pentosidine was not associated with MMPs or TIMP-1. CONCLUSIONS: We showed independent associations between several AGEs and markers of the MMP-TIMP system, which indicate specific AGE-MMP/TIMP-1 interactions potentially contributing to vascular complications in patients with type 1 diabetes.
Authors: William H Hoffman; Cornelia D Cudrici; Dallas Boodhoo; Alexandru Tatomir; Violeta Rus; Horea Rus Journal: Exp Mol Pathol Date: 2019-04-13 Impact factor: 3.362
Authors: J A F Demandt; L J Dubois; K van Kuijk; M Zaťovičová; H Jin; S Parkkila; S W van der Laan; L Jelenska; B M E Mees; C P M Reutelingsperger; K B J M Cleutjens; C J H van der Kallen; C G Schalkwijk; M M J van Greevenbroek; E A L Biessen; G Pasterkamp; S Pastoreková; C D A Stehouwer; J C Sluimer Journal: Sci Rep Date: 2021-01-11 Impact factor: 4.379