Contractile proteins and sarcoplasmic reticulum calcium-ATPase gene expression in the hypertrophied and failing heart.

The physiology of myocardial contractility has been studied for over a century, but only recently has molecular biology provided new insights into the mechanisms responsible for the alterations of contraction and relaxation observed during cardiac hypertrophy and heart failure. Pressure and volume overload produce in the myocyte both qualitative changes characterized by protein isoform switches and quantitative changes characterized by modulation of single genes through a mechanogenic transduction the pathways of which are largely unknown. The qualitative changes involve differential expression of multigene families of contractile proteins, especially myosin heavy chain (MHC) and actin. All situations of pressure overload, or of combined pressure and volume overload activate the beta-MHC gene and deactivate the alpha-MHC one, which leads to a slower, more efficient contraction. In rat, pressure overload transitorily activates the alpha-skeletal actin gene, and both the timing and the distribution of the newly formed beta-MHC and alpha-skeletal actin mRNAs differ. We recently found that the isoactin pattern is the same in patients with end-stage heart failure as that of control human hearts. Moreover, both in rat and human, expression of isomyosins and isoactins are not coordinated, neither during ontogeny nor senescence. All this suggests the existence of several regulatory mechanisms activated during normal cardiac growth or by a mechanical trigger, and preliminary results indicate that it is possible to perform nuclear run-on assays in order to analyze the transcriptional step of these isogenes.(ABSTRACT TRUNCATED AT 250 WORDS)