Left ventricular mechanical properties post-myocardial infarction and the role of matrix metalloproteinase-9

Coronary artery disease is the leading cause of death in the US. Myocardial infarction (MI) due to coronary artery disease is the leading cause of congestive heart failure. Understanding of the adaptation of left ventricle (LV) post MI is of paramount importance. Although significant progress has been made in understanding the pathophysiology of the LV remodeling process post MI, the underlying mechanisms of LV remodeling are not yet fully understood. Matrix Metalloproteinase-9 (MMP-9) is known to play an important role in the remodeling process of the heart. Decreased MMP-9 activity results in fewer ruptures of the myocardium in the affected area as well as less collagen formation. However, the underlying mechanisms are not clear. The objective of this study was to determine how the mechanical properties of the myocardium change with MMP-9 inhibition to determine the role of mechanical stress in the remodeling process. We hypothesized that after an MI, the myocardium of the LV remodels to compensate the damaged tissue, and therefore increase the LV stiffness, and that the LV myocardium of the MMP-9 null (knock out)mice will have lower stiffness than the C-57 mice.

The overall objective of this study was to determine the stiffness of a healthy and of an infarcted heart to uncover the changes in the different models, and to determine how the stiffness of the left ventricle changes when comparing the myocardium of C-57 mice to the MMP-9 null mice. Four test groups were examined: healthy wild type C-57, C-57 with an induced MI, healthy MMP-9 null, and MMP-9 null with an induced MI. The mechanical properties of the LV were determined for each group 7 days after the MI. By comparing the differences between these groups it was possible to determine the role of both MI and MMP-9 in changes of myocardium mechanical properties.

The results showed no significant change in stiffness for either type of mice before and after the MI. A big difference was seen in the change in end diastolic and end systolic stress (EDS & ESS) before and after the MI for both mice types (EDS PW P value = 0.0002; EDS SEP P value = 0.0013; ESS PW P value < 0.0001; ESS SEP P value = 0.0001). Once again, there was no difference in behavior between the C-57 and the MMP-9 null mice.

In conclusion, we found a big increase in stress at end diastole and end systole. No differences were found between the C-57 and the MMP-9 mice, and the infarcted myocardium showed only a trend of increase in stiffness in the C-57 mice, but no significant result. More research needs to be done to determine the exact mechanism of interaction between the MMP-9 protein and the infarct remodeling process, and the search for a three-dimensional model to test more accurate living conditions of the heart.