Structural alterations in the heart of integrin alpha 7 chain deficient mice

Specific interactions of the cells with the extracellular matrix are predominantly mediated by integrins, a family of heterodimeric transmembrane receptors, whose mechanotransductive properties and involvement as signal transducers in different cell activities is increasingly recognized. At least seven laminin-binding integrins are described, of which at least five ones are reported to be present in the heart. Our previous investigation on the distribution of the laminin binding integrins in murine and porcine myocardium indicated that integrin alpha 7 beta 1 is the mayor laminin integrin receptor in the heart, being localized at the surface of cardiomyocites with predominance at the myo-tendinous junction between papillary muscles and "chordae tendinae". To assess the significance of integrin alpha 7 chain, an ultrastructural investigation has been carried out on the heat of knock out mices obtained by generation of null allele of its gene (itga7) in the germline of mice by homologous recombination in embryonic stem cells (U. Mayer et al., Nat Genet, 17: 318-323, 1997). Myocardium appeared to be affected by generalized hypertrophia, that was more marked for ventricular walls. In particular, this alteration gave rise to overgrowth of connective tissue associated with severe degenerative changes in the papillary muscles, such as dramatic myofilament loss and sarcomer dissociation, and topical detachments between degenerating cardiomyocytes. At the myotendinous junctions, we observed an abnormous increase in the interdigitations between cardiomiocyte tips and "chordae tendinae", associated with abnormal thickening of basal laminae and accumulation of intracytoplasmic material. These data support the concept that integrin alpha 7 beta 1 is involved in proper anchorage of cardiomyocytes to the extracellular matrix, as for skeletal myofibers, dictating their mechanical performance. Moreover, this integrin seems to be implied in a number of additional roles correlating with cardiomyocyte functionality and cell-to-cell adhesiveness.