(Circulation. 2002;105:8.)
© 2002 American Heart Association, Inc.
Editorials |
Still Stressed Out but Doing Fine
Normalization of Wall Stress Is Superfluous to Maintaining Cardiac Function in Chronic Pressure Overload
From the Center for Cardiovascular Development and Department of Medicine (M.S.), and the Departments of Molecular and Cellular Biology and Molecular Physiology and Biophysics (M.D.S.), Baylor College of Medicine, Houston, Tex.
Correspondence to Michael D. Schneider, MD, Center for Cardiovascular Development, Baylor College of Medicine, One Baylor Plaza, Room 506D, Houston, TX. E-mail michaels@bcm.tmc.edu
Key Words: Editorials • hypertrophy • stress • cardiac output
Classically, myocardial hypertrophy is viewed as a long-term adaptive response of cardiac muscle to altered mechanical loading conditions, in which increasing wall thickness serves as the means to restore wall stress to normal, obeisant to the law of Laplace.1 The concept of local biomechanical stress as an instigator for this has been made clear through animal models, studies of cardiac muscle cells stretched in tissue culture, and long-standing clinical wisdom as with obstruction to right versus left ventricular outflow, respectively. Perhaps the most nebulous aspect of load-induced hypertrophy remains the exact identity of the initial mechanoreceptors—mechanical sensor(s) that become activated by a hemodynamic burden — although molecules that physically connect the cytoskeleton to the cell’s extracellular environment are among the prime candidates, including integrins and focal adhesion kinases. Much more is known of the intracellular signaling pathways that lie biochemically and genetically downstream from these initiating events, such as the secretion of preformed growth factors and cytokines, acting in autocrine or paracrine fashion, as well as the upregulation of the production of such proteins locally within the heart.1–3 In the context of whole-animal and clinical physiology, systemic effects, including an increase in catecholamines, also come into play. These multiple signals (ligand-dependent and overlaid on those induced by load itself) are transmitted to the cell nucleus via an intricate web of interlinked protein kinases, phospholipid kinases, and protein phosphatases.1–3 Beyond just increased mass, the specific long-term transcriptional responses to load entail a myriad of quantitative and qualitative changes in cardiac gene
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