Abstract 13961: Timing of Collagen Matrix Delivery Has Effect on Inflammation, Apoptosis, Angiogenesis and Preservation of Cardiac Function Following Myocardial Infarction
Background: Injectable biomaterials are emerging as promising regenerative therapies for treating myocardial infarction (MI). However, studies are lacking which evaluate the influence of timing of delivery on their therapeutic effect. In this study, we sought to identify an ideal time for delivery of a collagen matrix post-MI.
Methods/Results: C57BL/6J mice underwent LAD ligation to induce MI. Mice then received myocardial injections of PBS or collagen matrix delivered at 3h, 1wk or 2wk post-MI. Analyses were performed at 1 month post-treatment. Mice treated with matrix at 3h had smaller infarcts (30.7%) compared to all other groups (≥49.6%, p<0.05). Using echocardiography, mice with 3h matrix treatment had greater left ventricular ejection fraction (LVEF; 45.1±2.3%) compared to mice treated with matrix at 1wk (33.1±1.7%) or 2wk (24±2.7%; p<0.0002). LVEF was also greater in mice treated with collagen matrix delivered at 3h and 1wk compared to their PBS controls (29.6±2.4% and 27.1±1.4%, respectively), whereas 2wk treatment delivery did not improve cardiac function. A subset of 3h matrix-treated mice was maintained up to 3 months and %LVEF was maintained throughout this period (42.9±3.8%). Matrix treatment at 3h or 1wk increased the number of CD31+ vessels (p<0.05) and SMA+ arterioles (p<0.001) in the infarct compared to PBS. Treatment at 2wk did not improve tissue vascularity. Matrix treatment at 3h and 1wk reduced the number of invading CD68+ macrophages (p<0.01 vs. PBS), while the production of MIP[[Unable to Display Character: ‐]]1γ, RANTES, MIP-1α and sTNFRs inflammatory cytokines was reduced in macrophages cultured on the matrix in vitro (p<0.05). Mice treated with matrix at 3h had a 52% reduction in the number of apoptotic cells (active caspase-3+) in the infarcted myocardium (p<0.005 vs. 3h PBS and 1wk matrix), whereas 1wk matrix treatment only trended towards a reduction (by 16%; p=0.1 vs. 1wk PBS).
Conclusion: This is the first study to evaluate the effect of timing of collagen matrix delivery on the efficacy to treat MI. Matrix treatment significantly preserves cardiac function post-MI and the effect is significantly enhanced the earlier the hydrogel is delivered. Preservation may be mediated by reducing apoptosis, modulating inflammation and preserving tissue vascularity.
- © 2013 by American Heart Association, Inc.