Mechanotransduction in cardiomyocyte hypertrophy.

Abstract

The study of ventricular hypertrophy has recently been a fruitful research area. From studies principally in neonatal rat ventricular myocytes in primary culture but now increasingly in transgenic mice, the molecular mechanisms involved in this important pathophysiological adaptation are becoming clearer.1 In culture, cardiomyocyte hypertrophy is characterized by numerous transcriptional and morphological changes, including increased expression of atrial and B-type natriuretic peptides (ANP and BNP, respectively), increased β-myosin heavy chain (β-MHC) expression, and increased sarcomere deposition.1 Similar changes are evident in hypertrophied hearts in vivo, where increased sarcomere deposition in particular allows cardiomyocytes to accommodate demands for elevated contractile power. In vivo, pathological or experimental left ventricular hemodynamic overload induces patterns of hypertrophy that can be broadly divided into concentric or eccentric. In concentric (pressure-overload) hypertrophy, peak-systolic and end-diastolic pressures are increased, but meridional ventricular wall stress is normal throughout the cardiac cycle, the additional wall stress being counterbalanced by wall thickening in the absence of chamber enlargement. In eccentric (volume-overload) hypertrophy, chamber volume is enlarged, and wall thickness is increased approximately in proportion to the increase in chamber diameter. End-diastolic pressure and wall stress are increased, but peak systolic pressure and wall stress are normal. The orientation of cardiomyocytes in heart is primarily circumferential. Thus, cardiomyocytes from pressure- or volume-overloaded hearts differ in their relative dimensions. Cross-sectional area is proportionally expanded over length in pressure overload, whereas length is proportionally increased in volume overload. Sarcomere deposition parallel to the long axes of cells is greater in pressure overload than in volume overload, in which deposition of sarcomeres in series predominates. Changes in gene and protein expression in vivo may not be identical in the 2 paradigms. One study showed that although increases in prepro-ANP mRNA are comparable, increases in β-MHC mRNA occur only in pressure overload2 …