New therapies for pulmonary arterial hypertension: an update on current bench to bedside translation.
BACKGROUND
Treatments of pulmonary arterial hypertension (PAH) that have so far proven efficacious are all based on the restoration of endothelium control of pulmonary vascular tone and structure, by administration of prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. However, results remain unsatisfactory, with persistent high mortality, insufficient clinical improvement and no convincing report of any reversal of the disease process.


METHODS
New antiproliferative approaches that aim to actively limit pulmonary vascular remodeling are being sought. Several such treatments have shown promise in experimental models and in preliminary clinical studies. Noteworthy among these are dichloroacetate, survivin antagonists, nuclear factor of activated T-cell inhibitors, PPAR-gamma agonists, tyrosine kinase inhibitors, Rho-kinase inhibitors, statins, vasoactive intestinal peptide, soluble guanylate cyclase stimulators/activators, adrenomedullin, elastase inhibitors, serotonin reuptake inhibitors, anti-inflammatory agents, and bone marrow-derived progenitor cells.


RESULTS
Update on various strategies targeting proliferative, inflammatory and regenerating processes currently under evaluation in patients with PAH.


CONCLUSIONS
In spite of favorable results in experimental models, none of these strategies has achieved the ultimate goal of curing PAH. Further developments will depend on progress made in our pathobiological understanding of the disease and carefully designed randomized, controlled trials.
Dewachter
Laurence
L
Free University of Brussels, Department of Physiology, Faculty of Medicine, Erasme Campus CP 604, Lennik Road 808, B-1070 Brussels, Belgium. ldewacht@ulb.ac.be
Dewachter
Céline
C
Naeije
Robert
R
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000639:trends; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D019095:Point-of-Care Systems / Q000639:trends*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology
D000959:Antihypertensive Agents