title: Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy--a possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats?
abstract: Spontaneous valvulopathy has been described as nodular or segmental thickenings composed of fibromyxoid tissue in the subendocardium of various valve-leaflets in aging rats, but its pathogenesis and significance are incompletely understood. In this study, we examined the 5-hydroxytryptamine 2B receptor (5HT2BR) expression and characterization of extracellular matrix (ECM) components, and related these to the presence of valvulopathy in the mitral valve-leaflet (spontaneous mitral valvulopathy, SMV) of Sprague-Dawley (SD) rats. We also examined hearts from Fischer 344 (F344) rats treated with dl-amphetamine sulfate for 103 weeks to further explore the potential for drug-induced exacerbation of SMV. In SD rats, valve-leaflets with SMV exhibited a greater valve thickness, a higher amount of glycosaminoglycans, a lower amount of collagen and increased number of 5HT2BR-positive cells. Our data on morphology and ECM changes showed a striking similarity between SMV in SD rats and anorexigen-associated valvulopathy in humans, and increased 5HT2BR-positive cells in SMV implies that 5HT2BR may play a role in pathogenesis. Further, increased incidence and severity of SMV in F344 rats by treatment with dl-amphetamine suggest that a drug-induced exacerbation of SMV may exist in rats. However, additional research is needed to confirm a role for 5HT2BR in the pathogenesis of SMV in SD rats, and to further characterize the relationship between dl-amphetamine treatment and exacerbation of SMV in F344 rats.
authors.affiliation: Safety Assessment, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. chandi.s.elangbam@gsk.com
authors.forename: Chandikumar S
authors.initials: CS
authors.lastname: Elangbam
authors.forename: John G
authors.initials: JG
authors.lastname: Wehe
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Barton
authors.forename: David L
authors.initials: DL
authors.lastname: Krull
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Torrie
authors.initials: T
authors.lastname: Crabbs
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
mesh_terms: D000375:Aging / Q000473:pathology*; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis*; D008297:Male; D008943:Mitral Valve / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B / Q000032:analysis*
chemical_list: D006025:Glycosaminoglycans; D044403:Receptor, Serotonin, 5-HT2B; D000661:Amphetamine