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(Circulation. 2003;108:902.)
© 2003 American Heart Association, Inc.

Review: Current Perspective

Functional Consequence of Serotonin/5-HT_2B Receptor Signaling in Heart

Role of Mitochondria in Transition Between Hypertrophy and Heart Failure?

Canan G. Nebigil, PharmD, PhD; Luc Maroteaux, PhD

From the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, France.

Correspondence to Luc Maroteaux, PhD, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, 1 Rue Laurent Freies, BP 10142-67404 Illkirch Cedex, France. E-mail lucm@igbmc.u-strasbg.fr

Key Words: cardiomyopathy • genetics • hypertrophy • receptors • signal transduction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Para- and/or autocrine factors that interact with receptors coupled to G proteins of the Gq/11 families are implicated in the development of myocardial hypertrophy and apoptosis. Whether hypertrophy renders cardiac myocytes more sensitive or resistant to apoptosis is still controversial. A delicate balance may exist among hypertrophy, apoptosis, and heart failure. However, the factors involved in the transition from compensatory hypertrophy to heart failure have not been elucidated yet in the context of Gq-coupled pathways. Overexpressing serotonin Gq–coupled 5-HT_2B receptor in the mouse heart induces mitochondrial proliferation associated with hypertrophy, whereas ablation of this receptor leads to mitochondrial structural and functional impairments associated with myofibrillar breakdown and dilated cardiomyopathy. In this review, we discuss a novel role of mitochondria in the transition from hypertrophic to dilated cardiomyopathy that involves the Gq-coupled 5-HT_2BR signaling pathway.

Role of Serotonin in the Heart
Serotonin (5-hydroxytryptamine [5-HT]) was first isolated from blood and found to function as a vasoconstrictor. 5-HT is found in the following 3 main areas of the body: the intestinal wall (where it causes increased gastrointestinal motility), blood vessels (where it causes constriction of large vessels), and the central nervous system. Several lines of evidence suggest that 5-HT regulates cardiovascular function during embryogenesis and adulthood. 5-HT is secreted from enterochromaffin cells into the blood and stored in the platelets. Circulating 5-HT can also be taken up by sympathetic neurons and vascular endothelial cells and can be co-released. The effects of 5-HT in the cardiovascular system are complex: for example, 5-HT has been associated with bradycardia or . . . [Full Text of this Article]

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