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Monocyte matrix and ADAM metalloproteinase expression in type 2 diabetes after aspirin therapy
Mike Sampson1, Steven Wall, Mark Baugh
1Bertram Diabetes Research Unit, Norfolk and Norwich University Hospital NHS Trust, Norwich NR4 7UY, UK. mike.sampson@nnuh.nhs.uk
Abstract:
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.
Insights
Type 2 diabetes is linked to lower TIMP-1 mRNA in monocytes and a reduced plasma TIMP-1 to MMP-9 ratio, potentially increasing coronary plaque instability. Aspirin did not alter these markers in this study.
Area of Science:
- Biochemistry
- Vascular Biology
- Endocrinology
Background:
- Matrix metalloproteinases (MMPs) and ADAMs influence vascular plaque stability.
- Aspirin is known to suppress MMP expression and ADAM activity in vitro.
- Type 2 diabetes may affect the balance of these proteases, impacting cardiovascular risk.
Purpose of the Study:
- To investigate matrix metalloproteinase system (MMP), TIMP inhibitors (TIMPs), and ADAM metalloproteinases in type 2 diabetes.
- To assess the impact of oral aspirin therapy on monocyte and plasma levels of these molecules.
- To determine if these markers correlate with vascular plaque stability in type 2 diabetes.
Main Methods:
- Randomized prospective controlled study comparing type 2 diabetes patients (n=10) and controls (n=14).
- Measured peripheral venous monocyte MMP-9, TIMP-1, and ADAM mRNA and protein levels.
- Analyzed plasma MMP-9 and TIMP-1 concentrations before and after 14 days of 150mg daily oral aspirin or no intervention.
Main Results:
- Type 2 diabetes patients had significantly lower baseline monocyte TIMP-1 mRNA levels (p=0.0014).
- Plasma MMP-9 (p=0.027) and TIMP-1 (p=0.016) were higher in diabetes patients, with a lower TIMP-1:MMP-9 ratio (p=0.023).
- Oral aspirin therapy did not significantly affect any measured monocyte or plasma variables.
Conclusions:
- Type 2 diabetes is characterized by reduced monocyte TIMP-1 mRNA and a lower plasma TIMP-1 to MMP-9 ratio.
- This altered protease balance may promote coronary plaque instability in individuals with type 2 diabetes.
- Aspirin therapy did not significantly impact these specific molecular markers in this study population.
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