Common threads in cardiac fibrosis, infarct scar formation, and wound healing

Far from being merely an inert supporting scaffold, the cardiac extracellular matrix (ECM) is a dynamic structure that is in constant two-way communication with its embedded cells, such as myocytes and fibroblasts. Physical forces are integrated and transmitted by the ECM to these cells via cell–matrix interactions, resulting in activation of intracellular signaling pathways that both alter cell function and feed forward to induce changes in ECM structure via the release of matrix components or remodeling enzymes [1]. Information on the physical condition of the ECM is also encoded in the release of matrix-bound growth hormones or ECM constituents such as matrikines, providing another layer of complexity to the interaction of the ECM with its underlying cells.In response to injury such as myocardial infarction, the heart undergoes a wound-healing process that shows remarkable parallels with other wound-repair processes such as that occurring in the skin after physical trauma, despite the significant differences in the basic nature of these disparate tissues [2]. Fibrosis occurs when ECM synthesis outpaces degradation, and is a common pathological outcome in both the skin and the heart. A deeper understanding of wound healing and fibrosis may be obtained by examining these processes in both tissues, revealing the potential for mechanisms, pathways and possibly even therapies common to both.Following acute injury, wounded tissue undergoes a series of four stages aimed at repairing the injury and returning the tissue, as much as possible, to the pre-injured state (Figure 1) [3]. The mechanism of dermal wound healing is arguably the best understood at present, and is the focus of this section. The first stage of the healing process is hemostasis, consisting of coagulation and platelet activation at the site of injury. These events serve to rapidly stem blood loss by the formation of a fibrin clot, and occur shortly after the injury (typically within minutes). The coagul