AUTOCRINE AND PARACRINE REGULATION OF MYOCARDIAL-CELL GROWTH IN-VITRO- THE TGF-BETA PARADIGM

Over the past few years, there has been an increasing appreciation of the role that growth factors/cytokines play in cardiac growth/developm ent and the myocardial response to injury. This has derived, at least in part, from two observations: (a) that a number of these factors are expressed in response to myocardial stress, and (b) that some of thes e factors can stimulate myocardial growth in culture along with the ch aracteristic set of gene products that are associated with hypertrophy in vivo. Virtually all of the cells that make up the adult myocardium have at one time or another been reported to either be the source, th e site of action, or both, of many of these cytokines. Although the ce ll specificity of cytokine production is not critical to the understan ding of the complex nature of intracardiac cell-cell interactions as a mechanism of cardiac growth/development, this distinction does have s ome importance as myocardial cell culture gains increased popularity i n the research community Because there ave MO true cardiac muscle cell lines, all of the myocyte cultures used in these studies are, in esse nce, ''cocultures'' of cardiac myocytes and nonmyocytes (predominantly fibroblasts), with absolute numbers of these ''contaminating'' cells a function of plated cell density. As such, the cell specificity of so me substances on myocardial cell growth and transcriptional program (o f both myocytes and fibroblasts) is not always clear. This makes the c ritical examination of the expression (and effects) of these growth-pr omoting substances in culture of particular importance with attention to the specific culture conditions employed. The complexity of the sit uation in the heart is compounded by the observation that many of thes e substances have differential effects on the individual myocardial ce ll types and can induce the expression of other cytokines/cytokine rec eptors by these cells. In this report, the investigations published to date on the autocrine/paracrine effects of these factors on myocardia l cell growth in culture are reviewed. The complexity of the subject i s illustrated with the findings from our laboratory investigating one of the cytokines with growth-promoting effects on myocardial cells in culture, transforming growth factor beta (TGF beta). (C) 1996, Elsevie r Science Inc.