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

Increased microtubule density, through viscous loading of active myofilamen ts, causes contractile dysfunction of hypertrophied and failing pressure-ov erloaded myocardium, which is normalized by microtubule depolymerization. W e have found this to be based on augmented tubulin synthesis and microtubul e stability. We show here that increased tubulin synthesis is accounted for by marked transcriptional up-regulation of the beta 1- and beta 2-tubulin isoforms, that hypertrophic regulation of these genes recapitulates their d evelopmental regulation, and that the greater proportion of beta 1-tubulin protein may have a causative role in the microtubule stabilization found in cardiac hypertrophy.