Cellular mechanisms of cardiac hypertrophy

Abstract

Hypertrophy is the principal response of the heart to overload from any cause, including hypertension, myocardial infarction, valvar heart disease, and dilated cardiomyopathy. In the Framingham study, left ventricular hypertrophy was found on echocardiography in 15-20% of adults.1 This is an important observation because hypertrophy is a strong, independent predictor of cardiovascular death2 and is associated with diastolic dysfunction.3 Adult cardiac myocytes are highly specialised, terminally differentiated cells which have lost the ability to divide. The increase in heart muscle mass seen in cardiac hypertrophy occurs predominantly through an increase in myocyte size rather than number,4 though some claim evidence of mitotic division when the left ventricular mass exceeds 350 g.5 At a cellular level the events leading to cardiac hypertrophy can be broadly divided into three stages: extracellular hypertrophic stimulus; intracellular signal transduction; and activation of nuclear events which allow development of the hypertrophic phenotype.