Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction

Perlecan, a basal lamina proteoglycan, has been shown to interact with othe r extracellular matrix (ECM) components, especially type IV collagen, and i s thus involved in ECM formation. Perlecan has also been postulated to prom ote growth factor-receptor interactions, including the binding of basic fib roblast growth factor (bFGF) to its receptor, and to enhance mitogenesis an d angiogenesis. To test our hypothesis that perlecan is increased in the my ocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hyb ridization, Northern blotting, and immunohistochemistry. In situ hybridizat ion revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA s ignal distribution paralleled those for type IV collagen mRNA. Northern blo tting demonstrated increased expression of perlecan consistent with the obs ervations of in situ hybridization. Immunopositive staining for perlecan wa s observed in the infarct zone around granulation tissue on day 7 and in th e entire infarct zone on days 14-38. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with per lecan immunostaining, The present results demonstrated the expression of pe rlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the cont ribution of perlecan to the pathological course of myocardial infarction. ( C) 2000 Academic Press.