MATRIX METALLOPROTEINASE ACTIVITY EXPRESSION IN INFARCTED, NONINFARCTED AND DILATED CARDIOMYOPATHIC HUMAN HEARTS

In the normal myocardium matrix metalloproteinases (MMP) are present i n the latent form. To examine whether MMP are activated following infa rction or idiopathic dilated cardiomyopathy (DCM), we extracted and me asured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP a ctivity in infarcted left ventricle (LV), noninfarcted LV and right ve ntricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE typ e substrate gels embedded with type I gelatin (zymography). Accuracy o f the zymographic technique was shown for tissue samples as small as 0 .05 mg and was comparable to results obtained by a spectrophotometric method. After normalization for total protein concentration, we found 3 +/- 1% collagenase activity in normal atrial tissue which could be a ctivated to 80-90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV, on the other hand, collagenase activity was 85-95% and 10-20%, respectively, while 5-10% and 3-5%, respective ly, in noninfarcted LV. In DCM, collagenolytic activity in the endo an d epimyocardium was 75 +/- 5 and 35 +/- 5% in the LV and 35 rt 7 and 2 0 +/- 5% in the RV, respectively. Thus, in dilated failing human heart s secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and n oninfarcted portions of either ventricle with MI and in both ventricle s in DCM. This suggests that an activation of collagenase throughout t he myocardium may contribute to its remodeling that includes ventricul ar dilatation and wall thinning.