title: Cardiovascular remodeling and the peripheral serotonergic system.
abstract: Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects. The acute cardiovascular response to 5-HT, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT3, 5-HT1B/1D, 5-HT7and 5-HT2A/2Breceptors. The chronic contribution of 5-HT and its receptors (5-HT4and 5-HT2A/2B) in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and valve degeneration, will be explored in this review. Finally, through the analysis of the effects of sarpogrelate, some new aspects of 5-HT2Areceptor pharmacology in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells will also be discussed. The aim of this review is to emphasize the cardiac side effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system.
authors.affiliation: Laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), faculté de médecine, fédération de médecine translationnelle, laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), université et centre hospitalier de Strasbourg, 67085 Strasbourg, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Ayme-Dietrich
authors.affiliation: Laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), faculté de médecine, fédération de médecine translationnelle, laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), université et centre hospitalier de Strasbourg, 67085 Strasbourg, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Aubertin-Kirch
authors.affiliation: Inserm UMR-S 839, institut du Fer-à-Moulin, Sorbonne université, UPMC université Paris 06, 75005 Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Maroteaux
authors.affiliation: Laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), faculté de médecine, fédération de médecine translationnelle, laboratoire de neurobiologie et pharmacologie cardiovasculaire (EA7296), université et centre hospitalier de Strasbourg, 67085 Strasbourg, France. Electronic address: laurent.monassier@unistra.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005355:Fibrosis; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000009:adverse effects; D017366:Serotonin Receptor Agonists / Q000009:adverse effects; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin
keywords: Cardiac hypertrophy; Cardiac remodeling; Dégénérescence valvulaire; Fibrose; Fibrosis; Hypertrophie cardiaque; Remodelage cardiaque; Serotonin; Sérotonine; Valve degeneration