title: Serotonin transporter is not required for the development of severe pulmonary hypertension in the Sugen hypoxia rat model.
abstract: Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.
authors.affiliation: Departments of Pulmonology and.
authors.forename: Michiel Alexander
authors.initials: MA
authors.lastname: de Raaf
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Radboud University Medical Centre, Nijmegen, The Netherlands;
authors.forename: Yvet
authors.initials: Y
authors.lastname: Kroeze
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Radboud University Medical Centre, Nijmegen, The Netherlands;
authors.forename: Anthonieke
authors.initials: A
authors.lastname: Middelman
authors.affiliation: Departments of Pulmonology and Physiology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands;
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.affiliation: Department of Laboratory of Chemistry and metabolic diseases, University Medical Centre, Groningen, The Netherlands;
authors.forename: Helma
authors.initials: H
authors.lastname: de Jong
authors.affiliation: Departments of Pulmonology and.
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.affiliation: Department of Radiology, Medical UltraSound Imaging Center; Radboud University Medical Centre, Nijmegen, The Netherlands; and.
authors.forename: Chris
authors.initials: C
authors.lastname: de Korte
authors.affiliation: Pulmonary and Critical Care Medicine Division, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Radboud University Medical Centre, Nijmegen, The Netherlands;
authors.forename: Judith
authors.initials: J
authors.lastname: Homberg
authors.affiliation: Departments of Pulmonology and hj.bogaard@vumc.nl.
authors.forename: Harm Jan
authors.initials: HJ
authors.lastname: Bogaard
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D055786:Gene Knockout Techniques; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology*; D066253:Vascular Remodeling
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat
keywords: SuHx; experimental pulmonary hypertension; hypoxia; serotonin; serotonin transporter