2009 Southern Regional Meeting Abstracts

Purpose of Study: Experimental and clinical evidence confirm the role of inflammatory signalling in pathologic cardiac remodeling after acute myocardial infarction (AMI). Myeloid differentiation factor 88 (MyD88) is a naturally occurring protein that mediates the effects of multiple pro-inflammatory pathways, including interleukin-(IL)-1, IL-18, and the toll-like receptor family. IMG2005 is a novel oligopeptide that directly inhibits MyD88 homodimerization. We hypothesized that IMG2005 would prevent cardiac remodeling in a mouse model of AMI.
Methods Used: Fourteen ICR mice underwent permanent surgical coronary artery ligation. Mice received daily intraperitoneal injections of IMG2005 1 mg/kg (n=7) or NaCl 0.9% (n=7) for 14 days. Animals underwent transthoracic echocardiography at baseline, 7 days, and 14 days after surgery.
Summary of Results: IMG2005 attenuated left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) versus saline at 14 days (see figure). IMG2005 mice also exhibited partial inhibition of aneurysm score (3 vs 4, p<0.05) and a trend towards improved survival (p=0.06), but no observable changes in fractional shortening or ejection fraction at 14 days.
Conclusions: MyD88 inhibition with IMG2005 prevents unfavorable cardiac remodeling after experimental AMI in mice. To our knowledge, ours is the first model to investigate the effects of direct MyD88 inhibition in vivo. Pharmacologic inhibition of MyD88 may be a valuable therapeutic strategy in post-infarction remodeling and heart failure.