Abstract 912: Reverse Remodeling is Associated with Changes in Extracellular Matrix Proteases and Tissue Inhibitors after Mesenchymal Stem Cell (MSC) Treatment of Hypertrophic Cardiomyopathy
Introduction: Changes in ventricular extracellular matrix (ECM) composition of hypertrophic cardiomyopathy determine clinical outcomes. The effects of MSC transplantation upon ventricular remodeling and determinants of ECM composition in hypertrophic cardiomyopathy have not been studied.
Hypothesis: We hypothesized that MSC therapy has beneficial effects upon ventricular remodeling and ECM proteases and tissue inhibitors in a rat model of pressure overload cardiomyopathy.
Methods: Sprague-Dawley rats underwent aortic banding and were followed by echocardiography for development of heart failure. After a decrease in fractional shortening of 25% from baseline, intra-coronary randomized injection of 1 x 106 MSC (n=28) or PBS (n=20) was performed. Serial echocardiography was performed to identify reverse remodeling. Left ventricular protein analysis including matrix metalloproteinases (MMP-2, 3, 6 and 9) and tissue inhibitors of metalloproteinases (TIMP-1, 2 and 3) was performed after sacrifice on post-operative day 21 or 28. ANOVA was used for group comparison.
Results: Results are shown in Table 1⇓. MSC injection improved LV fractional shortening in the MSC group compared with the control group at 21 and 28 days. Both LVESD and LVEDD were improved at 28 days. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days.
Conclusions: In this model of hypertrophic cardiomyopathy, intra-coronary delivery of MSC during heart failure improved left ventricular reverse remodeling by 28 days. These echocardiographic findings were associated with decreased ventricular levels of MMP-3, 6 and 9 and TIMP-1 and 3 which were upregulated in the control group as heart failure progressed. These effects were most remarkable at 28 days following injection.
This study supports the potential use of MSC transplantation in the management of hypertrophic heart failure.