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French researchers identify target for incurable PAH disease

14.06.2011

Paris – Pulmonary arterial hypertension (PAH), a severe disease of the arterial blood vessels in the lungs, leads to chronically elevated pulmonary artery pressure and remodelling of the small pulmonary arteries (SMPs) as a prelude to right heart failure and premature death. Until today, there has been no cure for PAH. But now, French researchers under Jean-Sébastien Hulot at Université Pierre et Marie Curie have identified a new disease target (JCI, June, 13th, 2011). Their suggestion to inhibit the protein MRP4 (Multidrug resistance–associated protein 4, Abcc4) could provide a new way to treat individuals with PAH. In lung cell cultures from patients with clinical pulmonary hypertension, the protein was significantly over-expressed compared to healthy tissue and in mice under hyoxic conditions. Additionally, mice lacking MRP4 were protected from pulmonary hypertension. In addition, treatment of normal mice with the MRP4 blocker MK571 reversed pulmonary hypertension pointing to therapeutic potential in humans. MRP4 (Abcc4) regulates intracellular levels of cAMP and cGMP in arterial SMCs, implicating cyclic nucleotide-related signalling pathways in the mechanism underlying the protective effects of MRP4 inhibition.


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