PLASTICITY OF MYOCARDIAL PHENOTYPE DURING CARDIAC-HYPERTROPHY AND FAILURE

Cardiac hypertrophy and failure frequently cause complications in some cardiovascular diseases. Both conditions are associated with importan t modifications of the heart's contractile and endocrine functions, in duced by various changes in gene expression, which in turn are attribu table to chronic hemodynamic overload. Differential expression of the myosin heavy chain family leads to a disproportionate accumulation of the alpha form relative to the beta, which in turn causes slower but m ore efficient myocardial contraction. This transition occurs in the ro dent ventricle and human atrium. In the sarcomeric actin family, both the alpha-cardiac and alpha-skeletal isoforms are expressed in the mam malian ventricle in utero. After birth, the latter transiently accumul ates in the rodent ventricle at the acute phase of an experimental ove rload. In humans, alpha-skeletal actin accounts for over half of total actin ; this ratio remains the same during heart failure. In experime ntal models of hemodynamic overload, and during heart failure in human s, expression of Ca2+-ATPase in the sarcoplasmic reticulum is reduced. This decrease may partly account for the changes in cardiac relaxatio n observed in these circumstances. The atrial natriuretic factor gene in the ventricular myocardium is also activated, permitting the ventri cle to participate in the regulation of its loading conditions. Severa l mechanical and neurohumoral factors have been proposed as triggers f or this gene reprogramming. Research is currently focussed on signal t ransduction mechanisms, and in particular identification of the transc ription factors involved.