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.