title: Targeted therapies in pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies.
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.affiliation: INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Univ. Paris-Sud, Châtenay Malabry, France; AP-HP, Pharmacie, DHU Thorax Innovation, Hôpital Antoine Béclère, Clamart, France.
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Chaumais
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Sven
authors.initials: S
authors.lastname: Günther
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Girerd
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Cardiologie, DHU Thorax Innovation, Hôpital Antoine Béclère, Clamart, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Algalarrondo
authors.affiliation: National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Price
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Univ. Paris-Sud, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. Electronic address: marc.humbert@bct.aphp.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000818:Animals; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
keywords: ACVRL1; BMPR2; CCB; CO; CYP; EC; EGF; ENG; ERA; ET; Endothelial dysfunction; Endothelin receptor antagonist; FGF2; IPr; Kinase inhibitors; Kv; LVEF; MCT; NYHA; New York Heart Association; OS; PAH; PASMC; PDE-5; PDGF; PGI2; PGI2 receptor; PH; PVR; Prostacyclin; Pulmonary arterial hypertension; ROCK; ROS; RTK; RhoA/Rho kinase; SMC; SOD; TGF; TKI; TXA2; Type 5 phosphodiesterase inhibitors; VIP; VPAC; activin A receptor type II-like kinase-1; bone morphogenetic protein receptor type 2; cAMP; cGMP; calcium channel blockers; cardiac output; cyclic adenosine monophosphate; cyclic guanosine monophosphate; cytochrome P450; endoglin; endothelial cell; endothelin; endothelin receptor antagonist; epidermal growth factor; fibroblast growth factor 2; iPAH; idiopathic PAH; left ventricular ejection fraction; mPAP; mean pulmonary arterial pressure; monocrotaline; oxidative stress; phosphodiesterase type 5; platelet-derived growth factor; prostacyclin; pulmonary arterial hypertension; pulmonary artery smooth muscle cells; pulmonary hypertension; pulmonary vascular resistance; reactive oxygen species; receptor tyrosine kinase; sGc; smooth muscle cell; soluble guanylate cyclase; superoxide dismutase; thromboxane; transforming growth factor; tyrosine kinase inhibitor; vasoactive intestinal polypeptide; vasoactive intestinal polypeptide receptor; voltage-gated potassium channels