Expression of extracellular matrix proteins and the role of fibroblasts and macrophages in repair processes in ischemic porcine myocardium.

In the experimental model of coronary microembolization in pig hearts, the processes of wound healing and scar formation were studied. Methods employed were: electron microscopy, immunohistochemistry using monoclonal antibodies (against fibronectin, laminin, collagen I, III, and VI, chondroitin sulfate, and vimentin), and in situ hybridization with radioactively labeled RNA (histones, fibronectin) or cDNA (acidic fibroblast growth factor) probes. The following time course for expression of various proteins and their mRNAs was established: Mitotic activity was significant at 3 d as well as expression of fibronectin mRNA. Cellularity comprising blood borne cells and macrophages was high. At 7 d, fibronectin, laminin and collagen VI accumulation were pronounced, vimentin positive cells were numerous. At 4 weeks, collagen expression was prominent, but interstitial cells were still present. It is concluded that healing after myocardial necrosis passes through the classical phases of wound healing, i.e., granulation tissue formation and final scar formation. Different extracellular matrix proteins show a differing time course of expression, tumor necrosis factor-alpha (TNF-alpha) and acidic fibroblast growth factor (aFGF) produced by macrophages may be involved in inflammatory processes and angiogenesis. Scar formation is not yet completed at 4 weeks after injury.