CARDIAC INTEGRINS - THE TIES THAT BIND

An elaborate series of morphogenetic events must be precisely coordina ted during development to promote the formation of the elaborate three -dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its su rrounding environment regulate cardiac form and function. In vitro exp eriments from our laboratories provide direct evidence that cardiac ce ll shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integri n family of matrix receptors. Our data indicates that phenotypic infor mation is stored in the tertiary structure and chemical identity of th e ECM. This information appears to be actively communicated and transd uced by the alpha 1 beta 1 integrin molecule into an intracellular sig nal that regulates cardiac cell shape and myofibrillar organization. I n this study we have assessed the phenotypic consequences of suppressi ng the expression and accumulation of the alpha 1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of alpha(2) and alpha(5) integrin, int egrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein meta bolism. We also consider how biochemical signals and the mechanical si gnals mediated by the integrins may converge on common intracellular s ignaling pathways in the heart. Experiments with the whole embryo cult ure system indicate that angiotensin II, a peptide that carries inform ation concerning cardiac load, plays a role in controling cardiac loop ing and the proliferation of myofibrils during development. (C) 1998 b y Elsevier Science Inc.