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(Circulation. 2002;105:1152.)
© 2002 American Heart Association, Inc.

Editorial

Modulating Cardiac Hypertrophy by Manipulating Myocardial Lipid Metabolism?

Norbert Frey, MD; Eric N. Olson, PhD

From the Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Tex.

Correspondence to Eric N. Olson, Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148. E-mail eolson@hamon.swmed.edu

Key Words: Editorials • lipids • hypertrophy

The heart responds by hypertrophic growth to a variety of extrinsic stimuli, such as arterial hypertension and valvular heart disease, and to intrinsic contractile abnormalities resulting from sarcomeric gene mutations (reviewed in ¹). Although it initially may serve to adapt the myocardium to increased wall tension, prolonged hypertrophy frequently results in myocyte disarray and apoptosis, as well as ventricular fibrosis, with resulting progression to heart failure and sudden death.² A plethora of signaling cascades have been implicated in the activation of the hypertrophic gene program and cardiomyocyte growth.³ In contrast, relatively little is known about intrinsic mechanisms with the potential to inhibit or even reverse hypertrophy. The ability to harness such mechanisms offers promise in the development of novel therapeutic strategies to overcome the maladaptive consequences of hypertrophy.

See p 1240

Fuel generation in the adult myocardium relies on the oxidation of long chain fatty acids by the mitochondria for production of ATP. Cardiac hypertrophy is associated with a suppression of fatty acid oxidation and metabolic reversion of the heart toward increased glucose utilization, which is characteristic of the fetal heart.⁴ This metabolic shift can be viewed as an adaptive response, because it decreases myocardial oxygen consumption per mole of ATP generated. It is unclear at present, however, which maladaptive sequelae might result from chronically impaired oxidation of fatty acids in the heart, such as increased lipid accumulation.⁵

The genes involved in fatty acid oxidation are primarily regulated by a family of transcription factors that are referred to as peroxisome . . . [Full Text of this Article]

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