Signalling mechanisms of cardiac hypertrophy
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abstract
Recent epidemiological studies implicated left ventricular hypertrophy (LVH) as a premonitory symptom of mortality from many cardiovascular complications. Although hypertrophy by a chronic overload per se is not a pathological rather biological adaptive response of heart, in conditions such as essential hypertension, valvular heart diseases and myocardial infarction, but heart failure as a final form of hypertrophy is an obvious disease causing high mortality. Qualitative changes in genomic expression allow the hypertrophied cardiac fibre to develop a normal active tension to the increased load at the expense of its maximal shortening velocity (V-max), which are preceded by the temporary expression of proto-oncogenes, isogenes of proteins of contractile apparatus and the re-expression of 'fetal' isoforms. In recent years it has become clear that a variety of hormones are present in the heart and may participate in the genesis of cardiac hypertrophy. However, the molecular mechanisms remain unknown. Mechanical load or stretch of cardiac tissues has been identified as a growth stimulus, and humoral mechanisms such as the renin-angiotensin system and the sympathetic nervous system have been suggested to play a role in the regulation of cardiac cell growth and hypertrophy. Atrial natriuretic factor, nitric oxide and prostanoids may negate and balance the actions of various ionotropic agents. H-ras, G-proteins, proto-oncogenes and trans-acting factors have been identified for signal transduction in the regulation of cardiac gene program and hypertrophy.
