Integrative Physiology of Cardiac Hypertrophy

pp 377-388

Abstract

Although cardiac cellular hypertrophy is an adaptative process to increased workload, it is also one of the most influential clinical complications of cardiovascular disorders. It is well known that apart of patients with cardiac hypertrophy develop heart failure and that hypertrophy is associated with an increased mortality rate. Understanding the molecular mechanisms involved in cardiac hypertrophy is therefore extremely important. Mechanical stress directly induces gene expression as well as protein synthesis in cardiac myocytes. Im-mediate early genes and then fetal type genes are reinduced. Mechanical stress can also evoke a variety of signals in cardiomyocytes and the molecules which are involved in the signal transduction pathway of mechanical stress are similar to those which play important roles in many other cells stimulated by growth factors. So, once extra-cellular stimuli are received and converted into intracellular signals, signal transduction pathways are common among many cell types. Although many biochemical events which occur in cardiomyocytes subsequent to mechanical stretch have been clarified, one main intriguing question remains unanswered. How is mechanical stress converted into biochemical signals? In other words, what is the mechanoreceptor or the transducer for mechanical stress in cardiomyocites? It is assumed that mechanical stress directly activates enzymes such as phospholipase by placing the enzymes close to their phospholipid substances in the plasma membranes. The integrin-cytoskeleton complex may be an alternate candidate structure for a mechanoreceptor and a transducer. Thus, cells adhere to the extracellular matrix principally via interactions with integrins. Integrins are trans-membrane proteins consisting of one a and R chain. Since it is recognized that the nature of the extra-cellular matrix can influence cell behavior, this would suggest that binding by specific integrins may have specific functional consequences.  (...)