Signal and adaptational changes in gene expression during cardiac overload.
Chronic cardiac overload stimulates various quantitative and qualitative mechanisms of adaptation, some of them being species-specific. The signals responsible for these changes in gene expression are still speculative, nevertheless early modifications of the microtubular network have been reported. Soon after overload an increased expression of various genes coding for regulatory proteins has also been observed, this includes various oncogenes and the genes of several heat-shock proteins. Hypertrophy only, is non species-specific and is adaptational because it both multiples the number of contractile units and it lowers wall stress. The slowing of the shortening velocity allows the heart to produce normal tension, at a lower cost, and has different biological explanations depending on the species. In small rodent ventricles, the main but probably not the unique, determinant of this physiological parameter is an isomyosin shift from a high ATPase activity form V1 to a low activity form V3, discovered in our laboratory in 1979. This shift has a transcriptional origin and also occurs in atria in every mammalian including humans; nevertheless it has not been evidenced in the ventricles of humans, dog, cat or guinea-pig. In these species it is necessary to take into account other mechanisms, namely those involved intracellular calcium movements. The number of total, and possibly active, calcium channels is normal in rat overloaded heart suggesting that their synthesis is activated commensurate to the development of hypertrophy. The situation is more complex for other sarcolemma proteins such as the beta-adrenergic system and the Na+, K(+)-ATPase. For the latter there is presently some evidence that an isoenzymatic shift is likely to occur, at least in rats.