| First Author | Stöhr R | Year | 2014 |
| Journal | Atherosclerosis | Volume | 235 |
| Issue | 2 | Pages | 438-43 |
| PubMed ID | 24943223 | Mgi Jnum | J:271160 |
| Mgi Id | MGI:6279241 | Doi | 10.1016/j.atherosclerosis.2014.05.946 |
| Citation | Stohr R, et al. (2014) Loss of TIMP3 exacerbates atherosclerosis in ApoE null mice. Atherosclerosis 235(2):438-43 |
| abstractText | 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. |
