| Popis: |
Pulmonary arterial hypertension (PAH) is related to hypertrophic remodelling of the pulmonary vessels. Proliferation of pulmonary vascular smooth muscle cells (PA-SMCs) plays a key role in these changes.The PA-SMCs of patients suffering from idiopathic or secondary PAH are characterized by abnormally increased in vitro proliferation in response to serotonin or serum. Serotonin transporter (5-HTT), the mediator of the mitogenic activity of serotonin, and the expression of which is increased in the course of idiopathic or secondary PAH, is the basis of these effects. The overexpression of 5-HTT, selectively induced in vascular smooth muscle by transgenesis in the mouse, leads to the development of PAH. Treatment with selective 5-HTT inhibitors prevents or leads to complete reversal of experimental hypoxic or inflammatory PAH. The presence of polymorphism of the gene causing over expression of the protein and proliferation of PA-SMCs seems to determine the severity of certain types of human PAH, notably that complicating COPD.There is a potential therapeutic application of 5-HTT inhibitors in human PAH. A clinical study is currently taking place in France.The exploration of the role of 5-HTT and the mechanisms leading to its overexpression in PAH, as well as the interactions between 5-HTT and the BMPR2 gene, should lead to a significant increase in the understanding of the pathophysiology of the disease. |
