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

Autor: Dozio Nicoletta, Hughes David A, Worley Joanna R, Gavrilovic Jelena, Sampson Mike J
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: Cardiovascular Diabetology, Vol 6, Iss 1, p 21 (2007)
Druh dokumentu: article
ISSN: 1475-2840
DOI: 10.1186/1475-2840-6-21
Popis: 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 [adisintegrin and metalloproteinase] 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.
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