The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis

Background: Little is known about the involvement of matrix metalloproteinases (MMPs) in cardiac vascular remodelling induced by exercise. Our aim was to evaluate and localize MMP-2 and MMP-9's activities in relation to capillary proliferation in mouse hearts trained for 15, 30 and 45 days. Methods: Sixty-three mice were randomly assigned to 7 groups: four control sedentary groups (C0, C15, C30 and C45) and three groups trained by an endurance protocol (T15, T30 and T45). MMP-2 and MMP-9 were examined with zymography and immunostaining analyses. Capillary proliferation was evaluated counting the number of CD31-positive cells. Results: Different activity patterns of the latent form of both MMPs were found. Pro-MMP-9 increased after 15 days of training; whereas pro-MMP-2 gradually decreased after 30 and 45 days of training below the control groups. The latter was inversely correlated with capillary growth. MMP-9 was mainly localized in myocardiocytes and less evident in capillaries. Conversely, MMP-2 was more intense in capillary endothelial cells and slightly in myocardiocytes. Conclusions: A different spatiotemporal modulation of pro-MMP-2 and pro-MMP-9 activities has been detected in the myocardium during angiogenesis related to the aerobic training. These results can be useful to draw up training protocols for improving the performance of healthy and diseased human hearts.