Abstract 15824: Targeted Injection of a Biocomposite Material Alters Macrophage and Fibroblast Phenotype and Function Following Myocardial Infarction: Relation to LV Remodeling
Background: A recognized treatment target for the prevention of progressive LV remodeling following a myocardial infarction (MI) is to affect structural changes directly within the MI region. One such approach is through targeted injection of biocomposite materials, such as calcium hydroxyaptite (CHAM) into the MI region. However, the mechanisms by which targeted CHAM delivery alters the cellular biology of the evolving MI remodeling process remained unknown. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage (MAC) and fibroblast (FIBRO), were examined.
Methods and Results: MI was induced in adult pigs prior to randomization to CHAM injections (20, 0.1ml, targeted injections within MI region) or saline. At 7 or 21 days post-MI (n=6/time point/group), cardiac MRI was performed, followed by MAC and FIBRO isolation. Isolated MAC profiles for monocyte chemotactic MAC inflammatory protein-1 (MCP-1), as measured by rtPCR, increased at 7 days post-MI in the CHAM group compared to MI only (16.3± 6.6 vs 1.7± 0.6 Ct values, p<0.05) and were similar by 21 days post-MI. Temporal changes in FIBRO function and smooth muscle actin (SMA) expression, relative to referent control (n=5), occurred with MI (Figure). CHAM induced an early increase in FIBRO proliferation, migration, and SMA expression [[Unable to Display Character: –]] all indicative of FIBRO transformation. By 14 days, CHAM reduced LV dilation (diastolic volume: 75± 2 vs 97± 4 mL) and increased function (ejection fraction: 48± 2 vs 38± 2 %) compared to MI only (both p<0.05).
Conclusions: This study, for the first time, identified that early effects on macrophage and fibroblast differentiation occurred with injection of a biocomposite material within the MI, which was translated into reduced adverse LV remodeling. These unique findings demonstrate that biomaterial injections impart direct biological effects upon the MI remodeling process over and above any biophysical effects.
- © 2013 by American Heart Association, Inc.