Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis

The cardiac fibroblast is the most abundant cell type present in the myocar dium and is mainly responsible for the deposition of extracellular matrix ( ECM). important components of cardiac ECM include structural and adhesive p roteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overl oad of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to in vestigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechani cal stimuli to functional responses. Mechanical stimulation of cardiac fibr oblasts has been shown to result in activation of various signal transducti on pathways. The application of defined mechanical stimuli to cultured card iac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ul timately, for fibrosis to develop the overproduction of ECM must overcome a ny associated increases in collagenase activity. Mechanically induced upreg ulation of ECM production may follow direct or indirect pathways through th e autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is ne eded to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM. (C) 2000 Elsevier Science B.V. All rights reserved.