Abstract 964: Biglycan is Required for Adaptive Remodelling After Myocardial Infarction
Introduction: Biglycan (BGN) is a small leucine-rich proteoglycan that binds to and regulates collagen fibril formation. In addition, recently BGN has been shown to mediate a proinflammatory role during sepsis through activation of TLR-4 and TLR-2. After myocardial infarction (MI) both extensive remodelling of the extracellular matrix (ECM) and inflammation occurs. Whether BGN plays a role in the remodelling of the cardiac ECM and whether it might contribute to regulation of cardiac hemodynamic function is presently unknown. Therefore, it was investigated whether (i) BGN is detectable in human MI and (ii) whether BGN-deficiency alters hemodynamic function and survival after experimental MI in mice.
Methods: Biopsies of human myocardial infarct tissue were stained for collagen and BGN. MI was induced in mice with BGN-deficiency (BGN-KO) and wild type mice (WT) by ligation of the left anterior descending coronary artery and were compared to SHAM operated animals. At 5 days after MI the area at risk and the area of the infarct scar were determined. At 21 days after MI the left ventricular (LV) hemodynamic function was assessed by pressure-volume measurements in vivo to obtain LV enddiastolic pressure (EDP), LV enddiastolic volume (EDV), and LV-endsystolic volume (ESV).
Results and Discussion: All human infarct biopsies were positive for interstitial and perivascular BGN that strongly colocalized with collagen. Furthermore, BGN expression was increased at 3, 7 and 14 days after MI in mice. Notably, the infarct scar was significantly reduced in BGN-KO mice at 5 days. Thus absence of BGN might confer a protective function during the first days after MI. However, within 21 days post MI increased mortality occurred among the BGN-KO animals due to frequent ventricular ruptures. The surviving BGN-KO animals displayed severely impaired LV function at 21 days. This was shown by enlarged dilatation (ESV: 93±4.2 vs. 75±4.8 μl and EDV 96±4.4 vs. 111±4.2 μl; p<0.05) and elevated EDP (24±2.7 vs. 18±1.8 mmHg; p<0.05) after MI. In conclusion these data show that the presence of BGN is required for adaptive remodelling to stabilize the infarct scar and to preserve cardiac function.