Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis.
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.
Eddahibi
Saadia
S
INSERM U492, Département de Physiologie, Hôpital H Mondor, Créteil, France.
Adnot
Serge
S
D000818:Animals; D001067:Appetite Depressants / Q000009:adverse effects* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics
D001067:Appetite Depressants; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin