Low density lipoprotein from patients with Type 2 diabetes increases expression of monocyte matrix metalloproteinase and ADAM metalloproteinase genes

Worley, Joanna R., Hughes, David A., Dozio, Nicoletta, Gavrilovic, Jelena and Sampson, Mike J. (2007) Low density lipoprotein from patients with Type 2 diabetes increases expression of monocyte matrix metalloproteinase and ADAM metalloproteinase genes. Cardiovascular Diabetology, 6. ISSN 1475-2840

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Abstract

Aims: Type 2 diabetes is characterised by increased plasma concentrations of pro-inflammatory cytokines [such as tumour necrosis factor – alpha; TNF-α] and soluble forms of adhesion molecules involved in leukocyte – endothelial interactions. These molecules are synthesised as transmembrane proteins and the plasma soluble forms are generated by ectodomain cleavage from the cell surface by members of the ADAM [a d isintegrin a nd m etalloproteinase] proteinase family. We hypothesised that plasma low density lipoprotein [LDL] from subjects with Type 2 diabetes would influence in vitro monocytic ADAM and matrix metalloproteinase [MMP] gene expression differently compared to control LDL. Methods: We examined relative mRNA expression by real time PCR in a monocytic cell line [THP-1] cultured for 4, 8 and 24 hrs with human plasma LDL derived from subjects with [n = 5] or without [n = 4] Type 2 diabetes. Gene expression for MMP-1 and 9, and ADAM – 8, 15, 17 and 28 was studied. Results: Type 2 diabetes LDL significantly increased gene expression of MMP – 1 [p < 0.01] MMP – 9 [p < 0.001], and ADAM 17 [p < 0.05], – 28 [p < 0.01] and – 15 [p < 0.01] compared to control LDL. Type 2 diabetes LDL had disparate effects on inhibitors of MMP. Conclusion: These data suggest that Type 2 diabetes LDL could lead to increased adhesion molecule and TNF alpha cell surface shedding, and vascular plaque instability, by promoting increased expression of ADAM and MMP genes.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: EPrints Services
Date Deposited: 01 Oct 2010 13:36
Last Modified: 27 Apr 2022 22:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/152
DOI: 10.1186/1475-2840-6-21

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