Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control

Left, ventricular (LV) pressure (PO) or volume (VO) overload is accompanied by myocardial remodeling, but mechanisms that contribute to this progressi ve remodeling process remain unclear. The matrix metalloproteinases (MMPs) contribute to tissue remodeling in a:number of disease states. This study t ested the hypothesis that increased MMP expression and activity occur after the induction of an LV overload, which is accompanied by a loss;of endogen ous MMP inhibitory control. LV MMP zymographic-activity and species abundan ce were measured in dogs cinder the following conditions: acute PO induced by ascending aortic balloon inflation (6 h, n = 9), prolonged PO by aortic banding (10 days, n = 5), acute VO through mitral regurgitation secondary t o chordal rupture (6 h, n = 6), prolonged VO due to mitral regurgitation (1 4 days, n = 7), and sham-controls (n = 11). MMP zymographic activity in the 92-kDa region, indicative of MMP-9 activity, increased over threefold in a cute PO and VO and fell to control levels in prolonged PO and VO. The MMP-9 activity-to-abundance ratio increased by over fourfold with acute VO and t wofold in acute PO, suggesting a loss of inhibitory control. Endogenous MMP inhibitor content was unchanged with either PO or VO. Interstitial collage nase (MMP-1) content decreased by 50% with acute VO but not with acute PO. Stromelysin (MMP-3) levels increased by 40% with acute VO and increased by 80% with prolonged PO. Although changes in LV myocardial MMP activity and i nhibitory control occurred in both acute and prolonged PO and VO states, th ese changes were not identical. These results suggest that the type of over load stimulus may selectively influence myocardial MMP activity and express ion, which in turn would affect the overall LV myocardial remodeling proces s in LV overload.