Abstract 3537: Lack of Fibronectin EDA Prevents Adverse Cardiac Remodeling and Preserves Cardiac Function After Acute MI
Background Extracellular matrix may activate adverse inflammatory responses upon degradation. Fibronectin extra domain A (EDA), released after cell injury, is able to activate innate immunity via Toll-like receptor activation. Therefore, we hypothesized that in the absence of EDA, toll-like receptors will not be activated and cardiac function and geometry will be preserved after experimental MI.
Method and Results Left coronary artery ligation was performed in EDA−/− and wild-type (WT) mice. Overall and regional cardiac function and geometry were assessed using 9.4T mouse MRI, at baseline and 28 days after infarction. Data are presented as Mean±SEM. After 28 days, mean infarct size (as % of LV) was similar in both groups: 34.0±2.0% (p=0.818). Despite equal amount of scar formation of the left ventricle, EDA−/− mice showed significantly preserved LV geometry and enhanced cardiac function (Table 1⇓). Macrophage influx was reduced with 50% in EDA−/− mice (p=0.032) after 7 days. At 28 days, collagen deposition in the infarct area did not differ between EDA−/− and WT mice. However, significantly less collagen fibers were observed in the remote area of EDA−/− mice. No difference was seen in mRNA levels of procollagen-1 in both infarct and remote area. In contrary, procollagen-3 mRNA levels were highly suppressed in EDA−/− mice in both infarct and remote area (p<<med>0.001).
Conclusions We show for the first time that the lack of fibronectin EDA prevents adverse cardiac remodeling after MI in mice. This effect is partially due to decreased inflammation of the infarct area and decreased fibrosis of remote area, via altered collagen-3 production. Further studies are needed to understand the exact mode of action. Scavenging EDA after MI may be a therapeutic option in human.