Regulation of myosin heavy chain and actin isogenes during cardiac growth and hypertrophy.

Abstract

Expression of myosin heavy chain (MHC) and actin multigene families changes in mammals during cardiac growth and hypertrophy, but whether or not there is a common regulatory pathway is unclear. To address this question, we have looked at the alpha- and beta-MHC, and at the alpha-skeletal and alpha-cardiac actin (alpha-skel act and alpha-card act) isomRNA transitions during development and senescence, both in rat and human hearts. Since the precise amounts of each isoactin mRNA were not precisely known in the above situations, we first analyzed the time- course of accumulations of the two sarcomeric transcripts by primer extension assays, which allow an umambiguous quantification of the ratios of the two actin transcripts. In rats, both isogenes are expressed in-utero. alpha-skel act represents 40% of the total one week after birth, remains constant for 3 weeks, decreases to less than 5% at two months and does not re-accumulate thereafter. In humans, in contrast, alpha-skel act represents < 20% in-utero and in neonates, increases to 48% during the first decade after birth and becomes the predominant isoform of adult hearts. In rats beta-MHC mRNAs accumulate at birth, become undetectable at 3 weeks and reaccumulate to as much as 80% during senescence, and in humans beta-MHC mRNAs predominate throughout all developmental stages. These data show that in both species, the multigene families encoding the major contractile proteins are not coordinately regulated during development and aging.(ABSTRACT TRUNCATED AT 250 WORDS)