COORDINATE GENE-EXPRESSION DURING NEONATAL RAT-HEART DEVELOPMENT - A POSSIBLE ROLE FOR THE MYOCYTE IN EXTRACELLULAR-MATRIX BIOGENESIS AND CAPILLARY ANGIOGENESIS

Objective: Neonatal heart development is a period of active extracellu lar matrix deposition and capillary angiogenesis which follows the ces sation of ventricular myocyte proliferation The aim was to determine w hether coordinate expression of growth factors by the ventricular myoc yte could function to inhibit myocyte proliferation directly as well a s indirectly by paracrine stimulation of non-myocyte extracellular mat rix deposition and capillary angiogenesis. Methods: Immunohistochemist ry and northern blot hybridisations were performed on ventricular samp les from fetal to mature animals of the spontaneously hypertensive (SH R) and normotensive control Wistar Kyoto (WKY) strains. Results: Ventr icular expression of types I, III, and IV collagen genes reached their ''maximum'' within the first 2-3 postnatal weeks and then rapidly dec lined. Expression of TGFbeta3 and SPARC were found to precede and acco mpany the changes in extracellular matrix gene expression during this same developmental period. TGFbeta3 was immunolocalised to fetal cardi omyocytes with very limited expression in neonatal/adult non-myocytes. Associated with the neonatal expression of TGFbeta variants, transcri pts for the type 2 IGF receptor gradually declined over the first thre e postnatal weeks. Myocyte TGFbeta gene expression, latent TGFbeta rel ease, and paracrine mechanisms of action could be facilitated by resid ual type 2 IGF receptor expression to help mediate stimulation of non- myocyte extracellular matrix synthesis and deposition. Conclusions: Ex pression of select growth factors, growth factor receptors, and compon ents of the extracellular matrix appear to be highly coordinated durin g ventricular remodelling which occurs during neonatal heart developme nt. A paradigm is presented which integrates the expression patterns o f various myocyte derived stimuli and their postulated impact on forma tion of the structural components of the neonatal heart by modulation of myocyte and non-myocyte cell types.