WESTPORT, CT (Reuters Health) – Serotonin transporter activity plays a key role in the pathogenesis of the pulmonary artery smooth muscle cell proliferation observed in primary pulmonary hypertension (PPH), according to French researchers.
Dr. Serge Adnot, of the Institut National de la Santי et de la Recherche Mיdicale in Crיteil, and associates cultured pulmonary artery smooth muscle cells isolated from lung specimens in eight patients with PPH and from 21 control subjects with localized lung cancer.
As reported in The Journal of Clinical Investigation for October, cells from patients with PPH proliferated faster than did cells from control subjects when exposed to serum or serotonin. Such a differential effect was not seen when cells were exposed to growth factors.
Two serotonin transport inhibitors, fluoxetine and citalopram, had a dose-dependent inhibitory effect on proliferation of PPH cells exposed to serotonin and, to a lesser degree, cells exposed to serum. However, two serotonin receptor antagonists, ketanserin and GR127935, failed to provide such inhibition.
"Given that selective serotonin transporter inhibitors reduce smooth muscle cell proliferation, they may protect from the vascular lesions associated with PPH," the investigators suggest.
Genotype data on 89 patients with PPH showed that they more commonly possessed the L-allelic variant of the serotonin transporter gene promoter compared with 84 control subjects. The L-allelic variant is associated with transporter overexpression.
Further supporting the theory of a genetic basis for overexpression of the serotonin transporter was the finding that transporter activity was increased in the platelets of patients with PPH. In addition, Dr. Adnot's team points out, linkage studies have shown an association between the S-allelic variant of the transporter gene promotor and anxiety symptoms, suicidal behavior and severe alcoholism.
Dr. Marlene Rabinovitch, of the University of Toronto in Canada, suggests in an editorial that new therapies targeting serotonin responses may be used adjunctively to or as a replacement for the current standard PPH therapy, intravenous prostacyclin.
J Clin Invest 2001;108:1141-1150.
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