Abstract 18995: The Influence of Osteoglycin on Remodelling Processes After Myocardial Infarction
Background: After myocardial infarction, inflammatory processes as well as matrix metalloproteinases (MMP) and their inhibitors play a pivotal role in the formation of a resilient scar tissue. The proteoglycan osteoglycin (Ogn) has an important meaning for the composition of the extracellular matrix (ECM). In this study, we investigated the function of Ogn during remodelling processes of the ECM after myocardial infarction.
Methods: In wildtype mice (MI-control, n=48) and Ogn knockout-mice (MI-OgnKO, n=90), a left anterior descending artery occlusion was performed to induce myocardial infarction (MI). Functional parameters were assessed with magnetic resonance imaging (MRI Bruker, 7.05T) before and 7 days after induction of myocardial infarction. The expression of MMPs, tissue inhibitors of metalloproteinases (TIMP) and specific inflammatory mediators was assessed with quantitative real-time PCR. Immunohistochemistry was performed for quantitative analysis of MMPs, TIMPs and inflammatory cells. Furthermore, MMP 2 and 9 activity was detected by zymography.
Results: OgnKO mice showed a significantly decreased left ventricular function in comparison to MI controls. In OgnKO mice, a significantly higher mortality due to rupture of the left ventricle was detected after myocardial infarction (p<0.001). The mRNA expression and the protein amount of MMP 2 and 9 was significantly increased in OgnKO mice in comparison to MI controls after 7d. Additionally, an increased activity of MMP 2 and 9 and a significantly increased MMP2/TIMP2 ratio was found in OgnKO mice after MI. Expression of monocyte chemoattractive protein-1, interleukin-6 and interleukin-1b was upregulated in OgnKO mice 7d after infarction, compared to MI controls. OgnKO mice showed a significantly reduced infiltration of the infarct tissue with CD11b+ cells and F4/80+ macrophages in the inflammatory phase and a marked increase after 7d in comparison to MI controls.
Conclusion: The absence of Ogn results in an increased MMP expression and an altered MMP/TIMP ratio in the infarct area. Additionally, an impaired inflammatory response after myocardial infarction is evident. These are potential factors for an insufficient cardiac remodelling, which results in an increased rupture rate.
- © 2010 by American Heart Association, Inc.