PROGRESSIVE CHANGES IN MRNA OF RAT CARDIAC HEAVY CHAIN GENES WITH AGING

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Cardiac cell enlargement occurs in response to chronic arterial pressure overload in young rodents and with advanced adult age in normotensive rodents. Cardiac muscle of both senescent and pressure overloaded hearts exhibit a nearly identical pattern of altered cardiac excitation-contraction mechanisms, among which are a reduced contraction velocity, a reduction in the myosin ATPase activity, a marked increase in the expression of the V,(beta myosin heavy chain, MHC) and a reduction in V1 (alpha MHC) isoforms. In the heart of younger hypertensive adult rodents, this shift in MHC isoforms is due, in part at least, to changes in transcription of beta and alpha MHC genes. The present study was undertaken to determine whether the marked MHC shift occurring with age between adulthood and senescence is also associated with changes in MHC gene expression. Levels of mRNA coding for alpha and beta MHC were determined by Northern analysis and dot blots (oligonucleotide probes on pooled RNA purified from 6 hearts each of animals of a broad age range. The mRNA for beta MHC increased greater than fourfold from 1 to 24 months, the alpha mRNA for a MHC decreased by a proportional amount. Thus, the phenotypic, biophysical and biochemical cardiac contractile changes with adult aging are, in part at least, transcriptionally regulated.