The effect of matrix metalloproteinase inhibition on post-myocardial infarction cardiac function, remodeling and gene expression

Abstract

Background. Myocardial infarction (MI) is associated with ventricular hypertrophy and poorer survival. Matrix-metalloproteinases inhibition (M) has been implicated in post-MI remodeling. Methodology. Rat model, angiotensin-converting enzyme inhibitor (A) and M were administered [both(A/M); neither( -/- ); alone(A/-, -/M)] to both MI and Sham (Sh) operated rats. Function assessed by Langendorff apparatus and echocardiography, remodeling by echocardiograms and H E slides, collagen by Picosirius-red staining. DNA microarray analysis to determine changes in gene expression. Results. All data: Sh( -/- ), MI( -/- ), MI( -/M). Langendorff developed pressure, positive and negative dP/dT demonstrated similar trends. Statistics: significant difference (P lt; 0.05) between Sh( -/- ) and MI( -/M) and between MI( -/- ) and MI( -/M) and no significance between Sh( -/- ) and MI( -/- ) for any parameters. Echocardiography (function and morphometry), H E morphometry and collagen: P lt; 0.05 between MI and Sh but no difference between drug treatments. Microarray: altered gene expression classified in areas of apoptosis, anti-inflammatory, structural and novel. Conclusion. The results suggest similar improvements with both A and M on MI hearts.