Soluble RAGE but not endogenous secretory RAGE is associated with albuminuria in patients with type 2 diabetes |
| |
Authors: | Per M Humpert Zdenka Djuric Stefan Kopf Gottfried Rudofsky Michael Morcos Peter P Nawroth Angelika Bierhaus |
| |
Affiliation: | 1. School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK 2. Bertram Diabetes Research Department, Norfolk and Norwich University Hospital, Norwich, NR4 7UY, UK 3. Institute of Food Research, Norwich, NR4 7UA, UK
|
| |
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 disintegrin 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|