Doxorubicin-induced cardiomyopathy in rabbits altered plasma pro-MMP 2 and 9 activity over 45 days, but these changes were not associated with most echocardiographic parameters of cardiac remodeling.
Does doxorubicin-induced cardiomyopathy alter plasma and myocardial MMP 2 and 9 activity in rabbits?
In a rabbit model of doxorubicin-induced cardiomyopathy, plasma pro-MMP 2 and 9 activities are altered, but these changes do not strongly correlate with most echocardiographic parameters of cardiac remodeling.
ABSTRACT: Some studies have shown the role played by matrix metalloproteinases and their inhibitors in doxorubicin cardiotoxicity. In this study, we sought to investigate how plasma and myocardial MMP 2 and 9 perform in rabbits with doxorubicin-induced cardiomyopathy, searching for a correlation between the activity of these collagenases and cardiac remodeling. Cardiomyopathy was induced by doxorubicin given intravenously twice a week for six consecutive weeks. Plasma MMP activity and the echocardiogram were assessed at baseline, and at 15 and 45 days after first injection of doxorubicin. The myocardial activity of these enzymes was solely evaluated in nine rabbits at 45 days, and results were compared with nine healthy controls. We only identified the full-length forms of both MMP 2 and 9 throughout the study. The plasma pro-MMP 2 reduced along the deterioration of cardiac function, while the pro-MMP 9 increased significantly at T45 as compared to baseline and T15. A negative significant correlation was found to exist between the plasma activity of pro-MMP 2 and mitral E-to-mitral septal annular early diastolic velocity ratio, which is an estimate of mean left atrial pressure and congestion. Only pro-MMP 2 was found in myocardial samples, and mean activity of such enzyme was statistically lower than that recorded for healthy controls. Although no active form was documented for either collagenase, the duration of the treatment with doxorubicin played a role in the alteration of plasma pro-forms activity. However, these changes could not be associated with most echocardiographic parameters that are supportive of cardiac remodeling.
Nogueira et al. (Thu,) conducted a other in Doxorubicin-induced cardiomyopathy (n=18). Doxorubicin vs. Healthy controls was evaluated on Plasma and myocardial MMP 2 and 9 activity and correlation with cardiac remodeling. Doxorubicin-induced cardiomyopathy in rabbits altered plasma pro-MMP 2 and 9 activity over 45 days, but these changes were not associated with most echocardiographic parameters of cardiac remodeling.