Deficiency of Tissue Inhibitor of Matrix Metalloproteinase-1 Exacerbates LV Remodeling Following Myocardial Infarction in Mice

Abstract Recent,studies ,have ,directed ,the interests at modulating ,the heart failure process through,inhibition of activated ,MMPs. We hypothesized ,that a loss ,of MMP ,inhibitory control by TIMP-1 deficiency alters the course of post-infarction chamber ,remodeling and induced,chronic myocardial,infarction in wild-type and TIMP-1-/- mice. LV pressure- volume,loops obtained ,from wild-type and ,TIMP-1-/- mice ,demonstrated ,that LV end- diastolic volumes ,(LVEDVWT vs ,TIMP-/-: 52±4 vs ,71±6µl) and LV end-diastolic pressures (LVEDPWT vs,TIMP-/-: 9.0±1.2 vs 12.7±1.4mmHg) were significantly increased,in the TIMP- 1-/- mice,2 weeks,post-MI. LV contractility was,reduced,to a,similar degree,in both,the WTand TIMP-1-/- groups after MI, as indicated by a significant fall in the LV end- systolic pressure-volume ,relationship. Ventricular weight ,and ,cross-sectional areas ,of LVmyocytes,were ,significantly increased ,in TIMP-1-/- indicating that the hypertrophic response,was,more,pronounced.,The observed,significant loss of fibrillar collagen in the TIMP-1-/- controls may,have,been,an important,contributory factor for the observed,LV alterations in the ,TIMP-1-/- mice ,after MI. These ,findings demonstrate ,that TIMP-1