Monocyte matrix and ADAM metalloproteinase expression in type 2 diabetes after aspirin therapy.
The matrix metalloproteinase system (MMP and the TIMP inhibitors), and the ADAM metalloproteinases, have roles in maintaining vascular plaque stability and the shedding of cell surface molecules, such as TNF-alpha and adhesion molecules; aspirin suppresses MMP expression and ADAM activity from some cell lines in vitro. In a randomised prospective controlled study, we examined peripheral venous monocyte MMP-9, TIMP-1 and ADAM mRNA levels, and protein expression, in subjects with type 2 diabetes (n=10) and controls (n=14) before and after oral aspirin therapy (150mg daily for 14 days) or no active intervention. Baseline monocyte TIMP-1 mRNA levels were significantly lower in the diabetes group (p=0.0014), although monocyte MMP-9 mRNA, and MMP-9 and TIMP-1 protein expression after culture did not differ significantly between groups. Plasma MMP-9 (p=0.027) and TIMP-1 (p=0.016) concentrations were significantly greater, and the ratio of plasma TIMP-1:MMP-9 concentrations significantly lower, in the diabetes group (p=0.023). ADAM mRNA levels did not differ significantly between groups and oral aspirin therapy had no significant effect on any variable. Type 2 diabetes is characterised by reduced monocyte TIMP-1 mRNA levels, and a lower plasma MMP-9 to TIMP-1 protein ratio compared to controls, a pattern that would promote coronary plaque instability if reproduced within vascular plaque. Monocyte ADAM mRNA levels do not differ between group and oral aspirin has no significant effect on these variables.
Sampson
Mike
M
Bertram Diabetes Research Unit, Norfolk and Norwich University Hospital NHS Trust, Norwich NR4 7UY, UK. mike.sampson@nnuh.nhs.uk
Wall
Steven
S
Baugh
Mark
M
Worley
Jo
J
Davies
Isabel
I
Hughes
David
D
Gavrilovic
Jelena
J
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D051722:ADAM Proteins; D020780:Matrix Metalloproteinase 9; D001241:Aspirin