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Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis

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Author(s): Eddahibi Saadia | Adnot Serge

Journal: Respiratory Research
ISSN 1465-9921

Volume: 3;
Issue: 1;
Start page: 9;
Date: 2002;
Original page

Keywords: anorexigens | appetite suppressants | pulmonary hypertension | pulmonary vascular smooth muscle cells | serotonin transporter

ABSTRACT
Abstract Epidemiological studies have established that fenfluramine, D-fenfluramine, and aminorex, but not other appetite suppressants, increase the risk of primary pulmonary hypertension (PH). One current hypothesis suggests that fenfluramine-like medications may act through interactions with the serotonin (5-hydroxytryptamine [5-HT]) transporter (5-HTT) located on pulmonary artery smooth muscle cells and responsible for the mitogenic action of 5-HT. Anorexigens may contribute to PH by boosting 5-HT levels in the bloodstream, directly stimulating smooth muscle cell growth, or altering 5-HTT expression. We suggest that individuals with a high basal level of 5-HTT expression related to the presence of the long 5-HTT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms of appetite-suppressant-related PH.

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