Abstract 16257: Blocking of Wnt/Frizzled Signaling Stops the Dilatation of the Left Ventricle After Myocardial Infarction
Purpose: Current pharmacotherapy can not stop the left ventricular (LV) dilatation that occurs after myocardial infarction (MI). However, this would be of utmost clinical relevance to prevent the development of heart failure after MI. We showed previously that administration of the Wnt/frizzled blocker UM206 immediately after MI attenuates LV dilatation, but whether this intervention also can stop the progressive dilatation of an already dilated LV is subject of the present study.
Methods: Twenty three Swiss mice were subjected to MI by occlusion of the LAD. At 2 weeks post-MI, administration of the frizzled antagonist UM206 (Alzet osmotic minipump, 6µg/kg.day) was started until sacrifice at 5 weeks post-MI (late treatment). The results were compared with saline-treated animals that were sacrificed at 2 (n=8) and 5 (n=23) weeks post-MI. Echocardiography was performed using a Visualsonics Vevo770 device.
Results: The progressive increase of end-diastolic volume could effectively be stopped by UM206 treatment starting at week 3 after MI. This was accompanied by a doubling of the myofibroblast content of the infarct area. Ejection Fraction (EF) and dP/dt increased significantly in the late UM206 treatment group compared to saline.
Conclusions: Administration of the Wnt/frizzled blocking agent UM206 after 2 weeks of MI stops further LV dilatation, resulting in improved cardiac function. This may be explained by the increased myofibroblast numbers in the infarct area, as the contractile properties of these cells are likely to reduce dilatation of the infarct.
- © 2011 by American Heart Association, Inc.