title: Monoclonal endothelial cells in appetite suppressant-associated pulmonary hypertension.
abstract: Anorexigens such as aminorex fumarate and dexfenfluramine are associated with the development of severe pulmonary hypertension (PH), which clinically and histopathologically is considered indistinguishable from idiopathic or primary pulmonary hypertension (PPH). For the current study, we asked whether anorexigen-associated PH is characterized by monoclonal pulmonary endothelial cell proliferation (such as in PPH) or, alternatively, is associated with a polyclonal endothelial cell proliferation as found in secondary PH. Analysis of clonality by the human androgen receptor assay was performed in microdissected endothelial cells of plexiform lesions of two patients with anorexigen-associated PH. The four plexiform lesions of Patient 1 and the six of Patient 2 with anorexigen-associated PH exhibited a monoclonal expansion of pulmonary endothelial cells, with a mean clonality ratio of 0.03 +/- 0.01 SE. Our results indicate that appetite suppressant-associated PH is identical to PPH not only in clinical and histopathologic features but also, at a molecular level, in terms of the monoclonal nature of the endothelial cell proliferation. The anorexigens may accelerate the growth of pulmonary endothelial cells in patients with predisposition to develop PPH.
authors.affiliation: Department of Pathology, Division of Pulmonary Sciences and Critical Care Medicine, and Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Z
authors.initials: Z
authors.lastname: Radisavljevic
authors.forename: K R
authors.initials: KR
authors.lastname: Shroyer
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.forename: N F
authors.initials: NF
authors.lastname: Voelkel
mesh_terms: D000483:Alleles; D000635:Aminorex / Q000009:adverse effects / Q000031:analogs & derivatives; D001067:Appetite Depressants / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000473:pathology; D020372:Dexfenfluramine / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008875:Middle Aged; D011944:Receptors, Androgen / Q000032:analysis; D014960:X Chromosome / Q000187:drug effects
chemical_list: D001067:Appetite Depressants; D011944:Receptors, Androgen; D000635:Aminorex; D020372:Dexfenfluramine; C006559:aminorex fumarate