Mechanisms of post-myocardial infarction healing : from acute survival to chronic remodeling
- Author(s): Hunt, Darlene L.
- et al.
Acute survival and chronic healing after myocardial infarction (MI) depend on a myriad of processes that begin within hours of the injury and can continue in the form of remodeling even years thereafter. The myocardium has very little self-renewal capability, and tissue lost to MI is replaced with a collagenous scar. There are currently no clinical therapies that directly target myocardial healing, due in part to the pleiotropic effects and redundancy of signaling factors released after injury. In addition, some processes such as the inflammatory response are required for acute healing to proceed, but can also precipitate chronic deleterious remodeling and heart failure. A better understanding of the contributors to myocardial healing in both the acute and chronic phases is crucial in the search for clinical therapies that will improve the heart's response to MI injury. In this work, we investigated the mechanisms of post-MI healing by studying two murine models of altered myocardial wound repair. We first studied infarct scar formation in mice lacking a proteoglycan with a role in collagen fibril assembly, and found that this deficiency altered infarct scar structure and mechanical properties compared to controls. Next, we investigated acute and chronic healing in a strain capable of myocardial regeneration after cryoprobe injury. Our results showed that this strain survives the acute phase and heals in the chronic phase post-MI better than a control strain, and that these differences could be attributed to reduced acute apoptosis and inflammation. The results presented here provide new insight into the mechanisms of post-MI survival and healing, and will be useful for future studies designed to improve mammalian cardiac repair.