Cardiac myocyte remodeling in hypertrophy and progression to failure

Abstract

Contracting myocytes are highly variable in size and generally resemble elliptical cylinders in shape. Although their arrangement within the ventricular wall is rather complex, their length runs in a tangential manner, and their transverse axis runs transmurally. Consequently, it was proposed many years ago that changes in myocyte length (L) may contribute to chamber dilatation while myocyte transverse growth may be largely responsible for wall thickening during cardiac hypertrophy. In recent years, the development of more efficient, comprehensive, and precise methods of measuring cardiac myocyte dimensions has confirmed this. Specifically, pressure overloading during the compensated phase leads to concentric hypertrophy, which is characterized by an increase in myocyte cross-sectional area (CSA). Volume overloading during the compensated phase leads to a proportional increase in chamber diameter/wall thickness, which is characterized by increased L and CSA. Excessive myocyte lengthening (from series sarcomere addition) without a further change in CSA, appears to be the primary cellular alteration leading to chamber dilatation in the progression to failure. This event occurs long before the development of symptomatic heart failure. Understanding and targeting the associated abnormal signaling underlying this cellular change should have considerable clinical consequences.