Abstract
Background: Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of various proteases and receptors. We have previously shown TIMP3 to be downregulated in metabolic and inflammatory disorders, such as type 2 diabetes mellitus.We have now generated an ApoE-/-Timp3-/- mouse model in which, through the use of genetics, metabolomics and in-vivo phenotypical analysis we investigated the role of TIMP3 in the development of atherosclerosis. Methods and results: En face aorta analysis and aortic root examination showed that ApoE-/-Timp3-/- mice show increased atherosclerosis with increased infiltration of macrophages into the plaque. Serum concentration of MCP-1 were elevated in the serum of ApoE-/-Timp3-/- mice coupled with an expansion of the inflammatory (M1) Gr1+ macrophages, both in the circulation and within the aortic tissue. Targeted analysis of metabolites revealed a trend to reduced short chain acylcarnitines. Conclusions: Our study shows that lack of TIMP3 increases inflammation and polarizes macrophages towards a more inflammatory phenotype resulting in increased atherosclerosis.
Original language | English |
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Pages (from-to) | 438-443 |
Number of pages | 6 |
Journal | Atherosclerosis |
Volume | 235 |
Issue number | 2 |
DOIs | |
Publication status | Published - Aug 1 2014 |
Keywords
- Atherosclerosis
- Inflammation
- Metabolism
- Metabolomics
- TIMP3
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Medicine(all)