Abstract 15527: Targeted Myocardial Delivery of Gold Nanorods Modifies Fibroblast Transformation Following Myocardial Infarction - Relation to LV Remodeling
Background: Fundamental milestones in the progression of LV failure following myocardial infarction (MI) are adverse LV remodeling (defined as changes in LV geometry) and transformation of fibroblasts to myofibroblasts (MyoFBs). Strategies that alter this cellular transdifferentiation post-MI would hold therapeutic relevance. Preliminary studies determined that negatively charged polyelectrolyte gold nanorods (AuNRs) altered fibroblast transformation to MyoFBs evidenced by changes in smooth muscle actin (SMA) expression. This study tested the hypothesis that targeted AuNR injection within the MI region would alter MyoFB transformation, thus altering the course of post-MI remodeling.
Methods/Results: Adult pigs underwent MI induction (coronary ligation) and were randomized to receive MI only (n=5) or MI/AuNR injections (n=5; 9 100 uL injections; 1x109 AuNRs/injection). Referent matched controls (n=5) were included. At 14 days post-MI, echocardiography revealed that LV ejection fraction was reduced by 38±3% and MI thickness by 35±2% from baseline in the MI only group (both p<0.05). Importantly, these changes were significantly attenuated in the MI/AuNR group (22±2, 21±5 %, respectively, both p<0.05 vs MI only). Additionally, in the MI/AuNR group, gene expression analysis by real-time PCR array demonstrated significant decreases in genes associated with matrix remodeling, such as matrix metalloproteinase (MMP-14) and tissue inhibitors of MMPs (TIMP-2/-3). Moreover, relative expression of SMA was significantly (p<0.05) reduced in the MI/AuNR group, which was supported by a reduction in positive SMA staining within the MI region.
Conclusion: These results demonstrate that localized targeted injection of gold nanorods favorably modifies the post-MI remodeling process by influencing fibroblast transformation, a critical component of matrix remodeling, and provides proof of concept for this novel therapeutic strategy.
- © 2013 by American Heart Association, Inc.