Expression of collagen binding integrins during cardiac development and hypertrophy.

Abstract

The interaction between components of the extracellular matrix and the cell surface of cardiac myocytes appears to be regulated in part by receptors belonging to the integrin superfamily. The expression of the integrins was investigated at different stages of development of the heart as well as during cardiac hypertrophy. The characterization of the membrane proteins showed that a beta 1-integrin and associated alpha-chains were responsible for the interaction with collagen, laminin, and fibronectin. Immunoprecipitation data indicated that the presence of specific alpha-chains varied with development. These data were correlated with the ability of the isolated myocytes to attach to specific components of the extracellular matrix. The expression of the alpha 1-chain was prominently associated with the recognition of interstitial collagens. The presence of the alpha 1-chain was also associated with stages when collagen synthesis was increased, especially during fetal and neonatal growth and cardiac hypertrophy. Immunohistochemical localization with the antiserum against beta 1-integrin demonstrated its specific localization near the Z lines of cardiac myocytes. The localization both in vitro and in vivo indicated that the beta 1-integrin may play a role in myofibrillogenesis during development. The present immunohistochemical, cell adhesion, and biochemical data clearly indicate that integrins play a major role in the regulation of the interaction between cardiac myocytes and the extracellular matrix during development and disease.

Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip

“…Similarly, we observed a lower ratio of α-to β-MHC mRNA in stretched tissues, a commonly accepted indicator of heart disease (8, 9). We measured increased expression of genes encoding for several focal adhesion proteins, such as focal adhesion kinase and integrin α5, in response to stretch, which matches in vivo studies demonstrating upregulation of focal adhesion expression and signaling during the hypertrophic response to mechanical overload (39,(42)(43)(44). Although our results do not identify molecular mechanisms, they do motivate future studies to discover and validate therapeutic targets, such as focal adhesion signaling.…”

“…Focal adhesions are transmembrane, mechanosensitive protein complexes that couple the ECM to the cytoskeleton (41) and are commonly overexpressed in pathological hypertrophy (39,(42)(43)(44). Our microarray analysis revealed stretch-mediated upregulation of integrin α6 mRNA at 96 h, so we asked if other focal adhesion genes were up-regulated with mechanical loading (Fig.…”

Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity

“…This includes cardiac and skeletal myocytes, where the costameres, the counterpart of the focal adhesion complex, connect the sarcolemma to sarcomere Z lines through cytoskeletal proteins (4,12,15,25,33,38). Such structures provide a continuous path for mechanical signal transfer from the extracellular matrix to the sarcomere, nucleus, and internal organelles.…”

Pattern formation in chick feather development: Distribution of β1‐integrin in normal and scaleless embryos

“…There is some evidence to suggest that the pl-integrin recognized by the antiserum used in this study is a collagen receptor (Terracio et al, 1991a). If this pl-integrin is a collagen receptor, its role in stabilization of the feather pattern might be to immobilize dermal cells in the intergerm regions.…”

“…SDS-PAGE sample buffer was added to the sepharose beads with bound proteins; the sample was boiled for 5 min and subjected to SDS-PAGE and autoradiography as previously described (Gullberg et al, 1989). Precipitated proteins were identified by their molecular weight, co-migration with rat a chains (Terracio et al, 1991a), and by precipitation with mono-specific antibodies to the chicken a chains (Terracio et al, 1991b) …”