CELLULAR AND MOLECULAR-BIOLOGY OF CARDIAC-HYPERTROPHY

Cardiovascular system at the cellular level adapts to chronic haemodyn amic changes by altering gene expression, Cardiac cell-specific expres sions of many contractile protein genes are regulated at the transcrip tional level by the interaction of activator proteins with specific ci a-acting sequences, A number of positive and negative cia-acting eleme nts from upstream of the basal promoter region and some of their trans -acting protein binding factors have been characterized, Recent epidem iological studies implicated left ventricular hypertrophy (LVH) as a p remonitory symptom of mortality from many cardiovascular complications , Although cardiac hypertrophy by a chronic haemodynamic overload per se is not a pathological rather biological adaptive response of heart, heart failure as a final form of hypertrophy is an obvious disorder p roducing high mortality, Qualitative changes in the actin-myosin genom ic expression such as re-expression of fetal isoforms, through the ind uction of immediate-early genes (proto-oncogenes), allow the hypertrop hied cardiac fibre to develop a normal active tension to the sustained load at the cost of its maximal shortening velocity, thus inducing a pathological state, Multiple lines of evidence support the existence a nd functional integration of a variety of humoral factors within the h eart, and may participate in the genesis of LVH, The renin-angiotensin system (RAS) has been suggested to play a pivotal role in the regulat ion of cardiac cell growth and LVH. Other humoral mechanisms such as s ympathetic nervous system and endothelin vasoconstrictors have also be en implicated, Thus, the elucidation of the cellular and molecular bio logy of normal cardiac growth, development and hypertrophy may hopeful ly lead to the development of novel therapeutic strategies to cardiac failure.