Cardiac hypertrophic and developmental regulation of the beta-tubulin multigene family.

Increased microtubule density, through viscous loading of active myofilaments, causes contractile dysfunction of hypertrophied and failing pressure-overloaded myocardium, which is normalized by microtubule depolymerization. We have found this to be based on augmented tubulin synthesis and microtubule stability. We show here that increased tubulin synthesis is accounted for by marked transcriptional up-regulation of the beta1- and beta2-tubulin isoforms, that hypertrophic regulation of these genes recapitulates their developmental regulation, and that the greater proportion of beta1-tubulin protein may have a causative role in the microtubule stabilization found in cardiac hypertrophy.