Monoclonal endothelial cells in appetite suppressant-associated pulmonary hypertension

Anorexigens such as aminorex fumarate and dexfenfluramine are associated wi th 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 wheth er anorexigen-associated PH is characterized by monoclonal pulmonary endoth elial 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 expan sion 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 endothelia l cell proliferation. The anorexigens may accelerate the growth of pulmonar y endothelial cells in patients with predisposition to develop PPH.