Changes in titin and collagen underlie diastolic stiffness diversity of cardiac muscle

Small (N2B) and large (N2BA) cardiac titin isoforms are differentially expr essed in a species-specific and heart location-specific manner, To understa nd how differential expression of titin isoforms may influence passive stif fness of cardiac muscle we investigated the mechanical properties of mouse left ventricular (MLV) wall muscle (expressing predominantly the small titi n isoform), bovine left atrial (BLA) wall muscle (predominantly the large i soform), and bovine left ventricular (BLV) wall muscle (expressing small an d large isoforms at similar levels). Results indicate that the overall pass ive muscle stiffness of the muscle types varies nearly ten-ford, with stiff ness increasing in the following order: BLA, BLV and MLV. To investigate th e basis of the variation in the overall muscle stiffness, the contributions of titin and collagen to muscle stiffness were determined. Results showed that increased muscle stiffness results from increases in both titin- and c ollagen-based passive stiffness, indicating that titin and collagen change in a co-ordinated fashion. The expression level of the small titin isoform correlates with titin's contribution to overall muscle stiffness, suggestin g that differential expression of titin isoforms is an effective means to m odulate the filling behavior of the heart. (C) 2000 Academic Press.