[1]
Hoeper, M.M.; Bogaard, H.J.; Condliffe, R.; Frantz, R.; Khanna, D.; Kurzyna, M.; Langleben, D.; Manes, A.; Satoh, T.; Torres, F.; Wilkins, M.R.; Badesch, D.B. Definitions and diagnosis of pulmonary hypertension. J. Am. Coll. Cardiol., 2013, 62(25)(Suppl.), D42-D50. [http://dx.doi.org/10.1016/j.jacc.2013.10.032]. [PMID: 24355641].
[2]
Galiè, N.; Humbert, M.; Vachiery, J.L.; Gibbs, S.; Lang, I.; Torbicki, A.; Simonneau, G.; Peacock, A.; Vonk Noordegraaf, A.; Beghetti, M.; Ghofrani, A.; Gomez Sanchez, M.A.; Hansmann, G.; Klepetko, W.; Lancellotti, P.; Matucci, M.; McDonagh, T.; Pierard, L.A.; Trindade, P.T.; Zompatori, M.; Hoeper, M.; Aboyans, V.; Vaz Carneiro, A.; Achenbach, S.; Agewall, S.; Allanore, Y.; Asteggiano, R.; Paolo Badano, L.; Albert Barbera, J.; Bouvaist, H.; Bueno, H.; Byrne, R.A.; Carerj, S.; Castro, G.; Erol, C.; Falk, V.; Funck-Brentano, C.; Gorenflo, M.; Granton, J.; Iung, B.; Kiely, D.G.; Kirchhof, P.; Kjellstrom, B.; Landmesser, U.; Lekakis, J.; Lionis, C.; Lip, G.Y.; Orfanos, S.E.; Park, M.H.; Piepoli, M.F.; Ponikowski, P.; Revel, M.P.; Rigau, D.; Rosenkranz, S.; Voller, H.; Luis Zamorano, J. 2015 esc/ers guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the european society of cardiology (esc) and the european respiratory society (ers): Endorsed by: Association for European paediatric and congenital cardiology (aepc), international society for heart and lung transplantation (ishlt). Eur. Heart J., 2016, 37(1), 67-119. [http://dx.doi.org/10.1093/eurheartj/ehv317]. [PMID: 26320113].
[3]
Galiè, N.; Brundage, B.H.; Ghofrani, H.A.; Oudiz, R.J.; Simonneau, G.; Safdar, Z.; Shapiro, S.; White, R.J.; Chan, M.; Beardsworth, A.; Frumkin, L.; Barst, R.J. Tadalafil therapy for pulmonary arterial hypertension. Circulation, 2009, 119(22), 2894-2903. [http://dx.doi.org/10.1161/CIRCULATIONAHA.108.839274]. [PMID: 19470885].
[4]
Galiè, N.; Olschewski, H.; Oudiz, R.J.; Torres, F.; Frost, A.; Ghofrani, H.A.; Badesch, D.B.; McGoon, M.D.; McLaughlin, V.V.; Roecker, E.B.; Gerber, M.J.; Dufton, C.; Wiens, B.L.; Rubin, L.J. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation, 2008, 117(23), 3010-3019. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.742510]. [PMID: 18506008].
[5]
Benza, R.L.; Miller, D.P.; Barst, R.J.; Badesch, D.B.; Frost, A.E.; McGoon, M.D. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest, 2012, 142(2), 448-456. [http://dx.doi.org/10.1378/chest.11-1460]. [PMID: 22281797].
[6]
Pulido, T.; Adzerikho, I.; Channick, R.N.; Delcroix, M.; Galiè, N.; Ghofrani, H.A.; Jansa, P.; Jing, Z.C.; Le Brun, F.O.; Mehta, S.; Mittelholzer, C.M.; Perchenet, L.; Sastry, B.K.; Sitbon, O.; Souza, R.; Torbicki, A.; Zeng, X.; Rubin, L.J.; Simonneau, G.; Investigators, S. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N. Engl. J. Med., 2013, 369(9), 809-818. [http://dx.doi.org/10.1056/NEJMoa1213917]. [PMID: 23984728].
[7]
Bolli, M.H.; Boss, C.; Binkert, C.; Buchmann, S.; Bur, D.; Hess, P.; Iglarz, M.; Meyer, S.; Rein, J.; Rey, M.; Treiber, A.; Clozel, M.; Fischli, W.; Weller, T. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N′-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J. Med. Chem., 2012, 55(17), 7849-7861. [http://dx.doi.org/10.1021/jm3009103]. [PMID: 22862294].
[8]
Iglarz, M.; Binkert, C.; Morrison, K.; Fischli, W.; Gatfield, J.; Treiber, A.; Weller, T.; Bolli, M.H.; Boss, C.; Buchmann, S.; Capeleto, B.; Hess, P.; Qiu, C.; Clozel, M. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J. Pharmacol. Exp. Ther., 2008, 327(3), 736-745. [http://dx.doi.org/10.1124/jpet.108.142976]. [PMID: 18780830].
[9]
Gatfield, J.; Mueller, G.C.; Sasse, T.; Clozel, M.; Nayler, O. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One, 2012, 7(10)e47662 [http://dx.doi.org/10.1371/journal.pone.0047662]. [PMID: 23077657].
[10]
Wei, A.; Gu, Z.; Li, J.; Liu, X.; Wu, X.; Han, Y.; Pu, J. Clinical adverse effects of endothelin receptor antagonists: Insights from the meta-analysis of 4894 patients from 24 randomized double-blind placebo-controlled clinical trials. J. Am. Heart Assoc., 2016, 5(11), 5. [http://dx.doi.org/10.1161/JAHA.116.003896]. [PMID: 27912207].
[11]
Ghofrani, H.A.; Galiè, N.; Grimminger, F.; Grünig, E.; Humbert, M.; Jing, Z.C.; Keogh, A.M.; Langleben, D.; Kilama, M.O.; Fritsch, A.; Neuser, D.; Rubin, L.J. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med., 2013, 369(4), 330-340. [http://dx.doi.org/10.1056/NEJMoa1209655]. [PMID: 23883378].
[12]
Rubin, L.J.; Galiè, N.; Grimminger, F.; Grünig, E.; Humbert, M.; Jing, Z.C.; Keogh, A.; Langleben, D.; Fritsch, A.; Menezes, F.; Davie, N.; Ghofrani, H.A. Riociguat for the treatment of pulmonary arterial hypertension: A long-term extension study (PATENT-2). Eur. Respir. J., 2015, 45(5), 1303-1313. [http://dx.doi.org/10.1183/09031936.00090614]. [PMID: 25614164].
[14]
Hoeper, M.M.; Simonneau, G.; Corris, P.A.; Ghofrani, H.A.; Klinger, J.R.; Langleben, D.; Naeije, R.; Jansa, P.; Rosenkranz, S.; Scelsi, L.; Grünig, E.; Vizza, C.D.; Chang, M.; Colorado, P.; Meier, C.; Busse, D.; Benza, R.L. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur. Respir. J., 2017, 50(3), 50. [http://dx.doi.org/10.1183/13993003.02425-2016]. [PMID: 28889107].
[15]
Kuwano, K.; Hashino, A.; Asaki, T.; Hamamoto, T.; Yamada, T.; Okubo, K.; Kuwabara, K. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J. Pharmacol. Exp. Ther., 2007, 322(3), 1181-1188. [http://dx.doi.org/10.1124/jpet.107.124248]. [PMID: 17545310].
[16]
Morrison, K.; Studer, R.; Ernst, R.; Haag, F.; Kauser, K.; Clozel, M. Differential effects of Selexipag [corrected] and prostacyclin analogs in rat pulmonary artery. J. Pharmacol. Exp. Ther., 2012, 343(3), 547-555. [http://dx.doi.org/10.1124/jpet.112.197152]. [PMID: 22918043].
[17]
Sitbon, O.; Channick, R.; Chin, K.M.; Frey, A.; Gaine, S.; Galiè, N.; Ghofrani, H.A.; Hoeper, M.M.; Lang, I.M.; Preiss, R.; Rubin, L.J.; Di Scala, L.; Tapson, V.; Adzerikho, I.; Liu, J.; Moiseeva, O.; Zeng, X.; Simonneau, G.; McLaughlin, V.V.; Investigators, G. Selexipag for the treatment of pulmonary arterial hypertension. N. Engl. J. Med., 2015, 373(26), 2522-2533. [http://dx.doi.org/10.1056/NEJMoa1503184]. [PMID: 26699168].
[18]
Galiè, N.; Barberà, J.A.; Frost, A.E.; Ghofrani, H.A.; Hoeper, M.M.; McLaughlin, V.V.; Peacock, A.J.; Simonneau, G.; Vachiery, J.L.; Grünig, E.; Oudiz, R.J.; Vonk-Noordegraaf, A.; White, R.J.; Blair, C.; Gillies, H.; Miller, K.L.; Harris, J.H.; Langley, J.; Rubin, L.J.; Investigators, A. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N. Engl. J. Med., 2015, 373(9), 834-844. [http://dx.doi.org/10.1056/NEJMoa1413687]. [PMID: 26308684].
[19]
Galiè, N.; Hoeper, M.M.; Humbert, M.; Torbicki, A.; Vachiery, J.L.; Barbera, J.A.; Beghetti, M.; Corris, P.; Gaine, S.; Gibbs, J.S.; Gomez-Sanchez, M.A.; Jondeau, G.; Klepetko, W.; Opitz, C.; Peacock, A.; Rubin, L.; Zellweger, M.; Simonneau, G. Guidelines ESCCfP. Guidelines for the diagnosis and treatment of pulmonary hypertension: The task force for the diagnosis and treatment of pulmonary hypertension of the european society of cardiology (esc) and the european respiratory society (ers), endorsed by the international society of heart and lung transplantation (ishlt). Eur. Heart J., 2009, 30(20), 2493-2537. [http://dx.doi.org/10.1093/eurheartj/ehp297]. [PMID: 19713419].
[20]
McLaughlin, V.; Channick, R.N.; Ghofrani, H.A.; Lemarié, J.C.; Naeije, R.; Packer, M.; Souza, R.; Tapson, V.F.; Tolson, J.; Al Hiti, H.; Meyer, G.; Hoeper, M.M. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur. Respir. J., 2015, 46(2), 405-413. [http://dx.doi.org/10.1183/13993003.02044-2014]. [PMID: 26113687].
[21]
Coghlan, J.G.; Galiè, N.; Barberà, J.A.; Frost, A.E.; Ghofrani, H.A.; Hoeper, M.M.; Kuwana, M.; McLaughlin, V.V.; Peacock, A.J.; Simonneau, G.; Vachiéry, J.L.; Blair, C.; Gillies, H.; Miller, K.L.; Harris, J.H.N.; Langley, J.; Rubin, L.J. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann. Rheum. Dis., 2017, 76(7), 1219-1227. [http://dx.doi.org/10.1136/annrheumdis-2016-210236]. [PMID: 28039187].
[22]
Hassoun, P.M.; Zamanian, R.T.; Damico, R.; Lechtzin, N.; Khair, R.; Kolb, T.M.; Tedford, R.J.; Hulme, O.L.; Housten, T.; Pisanello, C.; Sato, T.; Pullins, E.H.; Corona-Villalobos, C.P.; Zimmerman, S.L.; Gashouta, M.A.; Minai, O.A.; Torres, F.; Girgis, R.E.; Chin, K.; Mathai, S.C. Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 2015, 192(9), 1102-1110. [http://dx.doi.org/10.1164/rccm.201507-1398OC]. [PMID: 26360334].
[23]
Mercurio, V.; Mukherjee, M.; Tedford, R.J.; Zamanian, R.T.; Khair, R.M.; Sato, T.; Minai, O.A.; Torres, F.; Girgis, R.E.; Chin, K.; Damico, R.; Kolb, T.M.; Mathai, S.C.; Hassoun, P.M. Improvement in right ventricular strain with ambrisentan and tadalafil upfront therapy in scleroderma pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 2018, 197(3), 388-391. [DOI: 10.1164/rccm.201704-0789LE]. [PMID: 28661697].
[24]
Garcia-Rivas, G.; Jerjes-Sánchez, C.; Rodriguez, D.; Garcia-Pelaez, J.; Trevino, V. A systematic review of genetic mutations in pulmonary arterial hypertension. BMC Med. Genet., 2017, 18(1), 82. [http://dx.doi.org/10.1186/s12881-017-0440-5]. [PMID: 28768485].
[25]
Austin, E.D.; Loyd, J.E. The genetics of pulmonary arterial hypertension. Circ. Res., 2014, 115(1), 189-202. [http://dx.doi.org/10.1161/CIRCRESAHA.115.303404]. [PMID: 24951767].
[26]
Johnson, D.W.; Berg, J.N.; Baldwin, M.A.; Gallione, C.J.; Marondel, I.; Yoon, S.J.; Stenzel, T.T.; Speer, M.; Pericak-Vance, M.A.; Diamond, A.; Guttmacher, A.E.; Jackson, C.E.; Attisano, L.; Kucherlapati, R.; Porteous, M.E.; Marchuk, D.A. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat. Genet., 1996, 13(2), 189-195. [http://dx.doi.org/10.1038/ng0696-189]. [PMID: 8640225].
[27]
McAllister, K.A.; Grogg, K.M.; Johnson, D.W.; Gallione, C.J.; Baldwin, M.A.; Jackson, C.E.; Helmbold, E.A.; Markel, D.S.; McKinnon, W.C.; Murrell, J. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat. Genet., 1994, 8(4), 345-351. [http://dx.doi.org/10.1038/ng1294-345]. [PMID: 7894484].
[28]
Harrison, R.E.; Flanagan, J.A.; Sankelo, M.; Abdalla, S.A.; Rowell, J.; Machado, R.D.; Elliott, C.G.; Robbins, I.M.; Olschewski, H.; McLaughlin, V.; Gruenig, E.; Kermeen, F.; Halme, M.; Räisänen-Sokolowski, A.; Laitinen, T.; Morrell, N.W.; Trembath, R.C. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J. Med. Genet., 2003, 40(12), 865-871. [http://dx.doi.org/10.1136/jmg.40.12.865]. [PMID: 14684682].
[29]
Trembath, R.C.; Thomson, J.R.; Machado, R.D.; Morgan, N.V.; Atkinson, C.; Winship, I.; Simonneau, G.; Galie, N.; Loyd, J.E.; Humbert, M.; Nichols, W.C.; Morrell, N.W.; Berg, J.; Manes, A.; McGaughran, J.; Pauciulo, M.; Wheeler, L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N. Engl. J. Med., 2001, 345(5), 325-334. [http://dx.doi.org/10.1056/NEJM200108023450503]. [PMID: 11484689].
[30]
Austin, E.D.; Ma, L.; LeDuc, C.; Berman Rosenzweig, E.; Borczuk, A.; Phillips, J.A., III; Palomero, T.; Sumazin, P.; Kim, H.R.; Talati, M.H.; West, J.; Loyd, J.E.; Chung, W.K. Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ Cardiovasc Genet, 2012, 5(3), 336-343. [http://dx.doi.org/10.1161/CIRCGENETICS.111.961888]. [PMID: 22474227].
[31]
Germain, M.; Eyries, M.; Montani, D.; Poirier, O.; Girerd, B.; Dorfmüller, P.; Coulet, F.; Nadaud, S.; Maugenre, S.; Guignabert, C.; Carpentier, W.; Vonk-Noordegraaf, A.; Lévy, M.; Chaouat, A.; Lambert, J.C.; Bertrand, M.; Dupuy, A.M.; Letenneur, L.; Lathrop, M.; Amouyel, P.; de Ravel, T.J.; Delcroix, M.; Austin, E.D.; Robbins, I.M.; Hemnes, A.R.; Loyd, J.E.; Berman-Rosenzweig, E.; Barst, R.J.; Chung, W.K.; Simonneau, G.; Trégouët, D.A.; Humbert, M.; Soubrier, F. Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension. Nat. Genet., 2013, 45(5), 518-521. [http://dx.doi.org/10.1038/ng.2581]. [PMID: 23502781].
[33]
Ranchoux, B.; Antigny, F.; Rucker-Martin, C.; Hautefort, A.; Péchoux, C.; Bogaard, H.J.; Dorfmüller, P.; Remy, S.; Lecerf, F.; Planté, S.; Chat, S.; Fadel, E.; Houssaini, A.; Anegon, I.; Adnot, S.; Simonneau, G.; Humbert, M.; Cohen-Kaminsky, S.; Perros, F. Endothelial-to-mesenchymal transition in pulmonary hypertension. Circulation, 2015, 131(11), 1006-1018. [http://dx.doi.org/10.1161/CIRCULATIONAHA.114.008750]. [PMID: 25593290].
[34]
Hopper, R.K.; Moonen, J.R.; Diebold, I.; Cao, A.; Rhodes, C.J.; Tojais, N.F.; Hennigs, J.K.; Gu, M.; Wang, L.; Rabinovitch, M. In pulmonary arterial hypertension, reduced bmpr2 promotes endothelial-to-mesenchymal transition via hmga1 and its target slug. Circulation, 2016, 133(18), 1783-1794. [http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020617]. [PMID: 27045138].
[35]
Stenmark, K.R.; Frid, M.; Perros, F. Endothelial-to-mesenchymal transition: An evolving paradigm and a promising therapeutic target in pah. Circulation, 2016, 133(18), 1734-1737. [http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022479]. [PMID: 27045137].
[36]
Machado, R.D.; Eickelberg, O.; Elliott, C.G.; Geraci, M.W.; Hanaoka, M.; Loyd, J.E.; Newman, J.H.; Phillips, J.A., III; Soubrier, F.; Trembath, R.C.; Chung, W.K. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol., 2009, 54(1)(Suppl.), S32-S42. [http://dx.doi.org/10.1016/j.jacc.2009.04.015]. [PMID: 19555857].
[37]
Evans, J.D.; Girerd, B.; Montani, D.; Wang, X.J.; Galiè, N.; Austin, E.D.; Elliott, G.; Asano, K.; Grünig, E.; Yan, Y.; Jing, Z.C.; Manes, A.; Palazzini, M.; Wheeler, L.A.; Nakayama, I.; Satoh, T.; Eichstaedt, C.; Hinderhofer, K.; Wolf, M.; Rosenzweig, E.B.; Chung, W.K.; Soubrier, F.; Simonneau, G.; Sitbon, O.; Gräf, S.; Kaptoge, S.; Di Angelantonio, E.; Humbert, M.; Morrell, N.W. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir. Med., 2016, 4(2), 129-137. [http://dx.doi.org/10.1016/S2213-2600(15)00544-5]. [PMID: 26795434].
[38]
Guignabert, C.; Bailly, S.; Humbert, M. Restoring BMPRII functions in pulmonary arterial hypertension: opportunities, challenges and limitations. Expert Opin. Ther. Targets, 2017, 21(2), 181-190. [http://dx.doi.org/10.1080/14728222.2017.1275567]. [PMID: 28001443].
[39]
Feng, F.; Harper, R.L.; Reynolds, P.N. BMPR2 gene delivery reduces mutation-related PAH and counteracts TGF-β-mediated pulmonary cell signalling. Respirology, 2016, 21(3), 526-532. [http://dx.doi.org/10.1111/resp.12712]. [PMID: 26689975].
[40]
Orriols, M.; Gomez-Puerto, M.C.; Ten Dijke, P. BMP type II receptor as a therapeutic target in pulmonary arterial hypertension. Cell. Mol. Life Sci., 2017, 74(16), 2979-2995. [http://dx.doi.org/10.1007/s00018-017-2510-4]. [PMID: 28447104].
[41]
Thompson, A.A.R.; Lawrie, A. Targeting vascular remodeling to treat pulmonary arterial hypertension. Trends Mol. Med., 2017, 23(1), 31-45. [http://dx.doi.org/10.1016/j.molmed.2016.11.005]. [PMID: 27989641].
[42]
Yang, K.; Wang, J.; Lu, W. Bone morphogenetic protein signalling in pulmonary hypertension: advances and therapeutic implications. Exp. Physiol., 2017, 102(9), 1083-1089. [http://dx.doi.org/10.1113/EP086041]. [PMID: 28449240].
[43]
Suen, C.M.; Mei, S.H.; Kugathasan, L.; Stewart, D.J. Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases. Compr. Physiol., 2013, 3(4), 1749-1779. [http://dx.doi.org/10.1002/cphy.c120034]. [PMID: 24265244].
[44]
Reynolds, A.M.; Holmes, M.D.; Danilov, S.M.; Reynolds, P.N. Targeted gene delivery of BMPR2 attenuates pulmonary hypertension. Eur. Respir. J., 2012, 39(2), 329-343. [http://dx.doi.org/10.1183/09031936.00187310]. [PMID: 21737550].
[45]
Long, L.; Ormiston, M.L.; Yang, X.; Southwood, M.; Gräf, S.; Machado, R.D.; Mueller, M.; Kinzel, B.; Yung, L.M.; Wilkinson, J.M.; Moore, S.D.; Drake, K.M.; Aldred, M.A.; Yu, P.B.; Upton, P.D.; Morrell, N.W. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat. Med., 2015, 21(7), 777-785. [http://dx.doi.org/10.1038/nm.3877]. [PMID: 26076038].
[46]
Guibert, C.; Marthan, R.; Savineau, J.P. Modulation of ion channels in pulmonary arterial hypertension. Curr. Pharm. Des., 2007, 13(24), 2443-2455. [http://dx.doi.org/10.2174/138161207781368585]. [PMID: 17692012].
[47]
Greenberg, B. Gene therapy for heart failure. J. Cardiol., 2015, 66(3), 195-200. [http://dx.doi.org/10.1016/j.jjcc.2015.02.006]. [PMID: 25818479].
[48]
Remillard, C.V.; Tigno, D.D.; Platoshyn, O.; Burg, E.D.; Brevnova, E.E.; Conger, D.; Nicholson, A.; Rana, B.K.; Channick, R.N.; Rubin, L.J.; O’connor, D.T.; Yuan, J.X. Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension. Am. J. Physiol. Cell Physiol., 2007, 292(5), C1837-C1853. [http://dx.doi.org/10.1152/ajpcell.00405.2006]. [PMID: 17267549].
[49]
Boucherat, O.; Chabot, S.; Antigny, F.; Perros, F.; Provencher, S.; Bonnet, S. Potassium channels in pulmonary arterial hypertension. Eur. Respir. J., 2015, 46(4), 1167-1177. [http://dx.doi.org/10.1183/13993003.00798-2015]. [PMID: 26341985].
[50]
Hadri, L.; Kratlian, R.G.; Benard, L.; Maron, B.A.; Dorfmüller, P.; Ladage, D.; Guignabert, C.; Ishikawa, K.; Aguero, J.; Ibanez, B.; Turnbull, I.C.; Kohlbrenner, E.; Liang, L.; Zsebo, K.; Humbert, M.; Hulot, J.S.; Kawase, Y.; Hajjar, R.J.; Leopold, J.A. Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension. Circulation, 2013, 128(5), 512-523. [http://dx.doi.org/10.1161/CIRCULATIONAHA.113.001585]. [PMID: 23804254].
[51]
Lipskaia, L.; Bobe, R.; Chen, J.; Turnbull, I.C.; Lopez, J.J.; Merlet, E.; Jeong, D.; Karakikes, I.; Ross, A.S.; Liang, L.; Mougenot, N.; Atassi, F.; Lompré, A.M.; Tarzami, S.T.; Kovacic, J.C.; Kranias, E.; Hajjar, R.J.; Hadri, L. Synergistic role of protein phosphatase inhibitor 1 and sarco/endoplasmic reticulum Ca2+ -ATPase in the acquisition of the contractile phenotype of arterial smooth muscle cells. Circulation, 2014, 129(7), 773-785. [http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002565]. [PMID: 24249716].
[52]
Aguero, J.; Ishikawa, K.; Hadri, L.; Santos-Gallego, C.G.; Fish, K.M.; Kohlbrenner, E.; Hammoudi, N.; Kho, C.; Lee, A.; Ibáñez, B.; García-Alvarez, A.; Zsebo, K.; Maron, B.A.; Plataki, M.; Fuster, V.; Leopold, J.A.; Hajjar, R.J. Intratracheal gene delivery of serca2a ameliorates chronic post-capillary pulmonary hypertension: A large animal model. J. Am. Coll. Cardiol., 2016, 67(17), 2032-2046. [http://dx.doi.org/10.1016/j.jacc.2016.02.049]. [PMID: 27126531].
[53]
Rhodes, C.J.; Wharton, J.; Boon, R.A.; Roexe, T.; Tsang, H.; Wojciak-Stothard, B.; Chakrabarti, A.; Howard, L.S.; Gibbs, J.S.; Lawrie, A.; Condliffe, R.; Elliot, C.A.; Kiely, D.G.; Huson, L.; Ghofrani, H.A.; Tiede, H.; Schermuly, R.; Zeiher, A.M.; Dimmeler, S.; Wilkins, M.R. Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 2013, 187(3), 294-302. [http://dx.doi.org/10.1164/rccm.201205-0839OC]. [PMID: 23220912].
[54]
Caruso, P.; Dempsie, Y.; Stevens, H.C.; McDonald, R.A.; Long, L.; Lu, R.; White, K.; Mair, K.M.; McClure, J.D.; Southwood, M.; Upton, P.; Xin, M.; van Rooij, E.; Olson, E.N.; Morrell, N.W.; MacLean, M.R.; Baker, A.H. A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples. Circ. Res., 2012, 111(3), 290-300. [http://dx.doi.org/10.1161/CIRCRESAHA.112.267591]. [PMID: 22715469].
[55]
Courboulin, A.; Paulin, R.; Giguère, N.J.; Saksouk, N.; Perreault, T.; Meloche, J.; Paquet, E.R.; Biardel, S.; Provencher, S.; Côté, J.; Simard, M.J.; Bonnet, S. Role for miR-204 in human pulmonary arterial hypertension. J. Exp. Med., 2011, 208(3), 535-548. [http://dx.doi.org/10.1084/jem.20101812]. [PMID: 21321078].
[56]
Shi, L.; Liao, J.; Liu, B.; Zeng, F.; Zhang, L. Mechanisms and therapeutic potential of microRNAs in hypertension. Drug Discov. Today, 2015, 20(10), 1188-1204. [http://dx.doi.org/10.1016/j.drudis.2015.05.007]. [PMID: 26004493].
[57]
Abenhaim, L.; Moride, Y.; Brenot, F.; Rich, S.; Benichou, J.; Kurz, X.; Higenbottam, T.; Oakley, C.; Wouters, E.; Aubier, M.; Simonneau, G.; Bégaud, B. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N. Engl. J. Med., 1996, 335(9), 609-616. [http://dx.doi.org/10.1056/NEJM199608293350901]. [PMID: 8692238].
[58]
Rothman, R.B.; Ayestas, M.A.; Dersch, C.M.; Baumann, M.H. Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Circulation, 1999, 100(8), 869-875. [http://dx.doi.org/10.1161/01.CIR.100.8.869]. [PMID: 10458725].
[59]
Hervé, P.; Launay, J.M.; Scrobohaci, M.L.; Brenot, F.; Simonneau, G.; Petitpretz, P.; Poubeau, P.; Cerrina, J.; Duroux, P.; Drouet, L. Increased plasma serotonin in primary pulmonary hypertension. Am. J. Med., 1995, 99(3), 249-254. [http://dx.doi.org/10.1016/S0002-9343(99)80156-9]. [PMID: 7653484].
[60]
Kéreveur, A.; Callebert, J.; Humbert, M.; Hervé, P.; Simonneau, G.; Launay, J.M.; Drouet, L. High plasma serotonin levels in primary pulmonary hypertension. Effect of long-term epoprostenol (prostacyclin) therapy. Arterioscler. Thromb. Vasc. Biol., 2000, 20(10), 2233-2239. [http://dx.doi.org/10.1161/01.ATV.20.10.2233]. [PMID: 11031209].
[61]
Hoyer, D.; Clarke, D.E.; Fozard, J.R.; Hartig, P.R.; Martin, G.R.; Mylecharane, E.J.; Saxena, P.R.; Humphrey, P.P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol. Rev., 1994, 46(2), 157-203. [PMID: 7938165].
[62]
Maclean, M.R.; Dempsie, Y. The serotonin hypothesis of pulmonary hypertension revisited. Adv. Exp. Med. Biol., 2010, 661, 309-322. [http://dx.doi.org/10.1007/978-1-60761-500-2_20]. [PMID: 20204739].
[63]
Sadoughi, A.; Roberts, K.E.; Preston, I.R.; Lai, G.P.; McCollister, D.H.; Farber, H.W.; Hill, N.S. Use of selective serotonin reuptake inhibitors and outcomes in pulmonary arterial hypertension. Chest, 2013, 144(2), 531-541. [http://dx.doi.org/10.1378/chest.12-2081]. [PMID: 23558791].
[64]
Chambers, C.D.; Hernandez-Diaz, S.; Van Marter, L.J.; Werler, M.M.; Louik, C.; Jones, K.L.; Mitchell, A.A. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N. Engl. J. Med., 2006, 354(6), 579-587. [http://dx.doi.org/10.1056/NEJMoa052744]. [PMID: 16467545].
[65]
Guignabert, C.; Raffestin, B.; Benferhat, R.; Raoul, W.; Zadigue, P.; Rideau, D.; Hamon, M.; Adnot, S.; Eddahibi, S. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation, 2005, 111(21), 2812-2819. [http://dx.doi.org/10.1161/CIRCULATIONAHA.104.524926]. [PMID: 15927991].
[66]
Marcos, E.; Adnot, S.; Pham, M.H.; Nosjean, A.; Raffestin, B.; Hamon, M.; Eddahibi, S. Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am. J. Respir. Crit. Care Med., 2003, 168(4), 487-493. [http://dx.doi.org/10.1164/rccm.200210-1212OC]. [PMID: 12773327].
[67]
Eddahibi, S.; Raffestin, B.; Pham, I.; Launay, J.M.; Aegerter, P.; Sitbon, M.; Adnot, S. Treatment with 5-HT potentiates development of pulmonary hypertension in chronically hypoxic rats. Am. J. Physiol., 1997, 272(3 Pt 2), H1173-H1181. [PMID: 9087590].
[68]
Morecroft, I.; Pang, L.; Baranowska, M.; Nilsen, M.; Loughlin, L.; Dempsie, Y.; Millet, C.; MacLean, M.R. In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension. Cardiovasc. Res., 2010, 85(3), 593-603. [http://dx.doi.org/10.1093/cvr/cvp306]. [PMID: 19736308].
[69]
Bhat, L.; Hawkinson, J.; Cantillon, M.; Reddy, D.G.; Bhat, S.R.; Laurent, C.E.; Bouchard, A.; Biernat, M.; Salvail, D. RP5063, a novel, multimodal, serotonin receptor modulator, prevents monocrotaline-induced pulmonary arterial hypertension in rats. Eur. J. Pharmacol., 2017, 810, 92-99. [http://dx.doi.org/10.1016/j.ejphar.2017.05.048]. [PMID: 28577964].
[70]
Janssen, W.; Schymura, Y.; Novoyatleva, T.; Kojonazarov, B.; Boehm, M.; Wietelmann, A.; Luitel, H.; Murmann, K.; Krompiec, D.R.; Tretyn, A.; Pullamsetti, S.S.; Weissmann, N.; Seeger, W.; Ghofrani, H.A.; Schermuly, R.T. 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure. BioMed Res. Int., 2015, 2015438403 [http://dx.doi.org/10.1155/2015/438403]. [PMID: 25667920].
[71]
Perros, F.; Dorfmüller, P.; Montani, D.; Hammad, H.; Waelput, W.; Girerd, B.; Raymond, N.; Mercier, O.; Mussot, S.; Cohen-Kaminsky, S.; Humbert, M.; Lambrecht, B.N. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 2012, 185(3), 311-321. [http://dx.doi.org/10.1164/rccm.201105-0927OC]. [PMID: 22108206].
[72]
Dorfmüller, P.; Perros, F.; Balabanian, K.; Humbert, M. Inflammation in pulmonary arterial hypertension. Eur. Respir. J., 2003, 22(2), 358-363. [http://dx.doi.org/10.1183/09031936.03.00038903]. [PMID: 12952274].
[73]
Nicolls, M.R.; Taraseviciene-Stewart, L.; Rai, P.R.; Badesch, D.B.; Voelkel, N.F. Autoimmunity and pulmonary hypertension: a perspective. Eur. Respir. J., 2005, 26(6), 1110-1118. [http://dx.doi.org/10.1183/09031936.05.00045705]. [PMID: 16319344].
[74]
Voelkel, N.F.; Tuder, R.M.; Wade, K.; Höper, M.; Lepley, R.A.; Goulet, J.L.; Koller, B.H.; Fitzpatrick, F. Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats. J. Clin. Invest., 1996, 97(11), 2491-2498. [http://dx.doi.org/10.1172/JCI118696]. [PMID: 8647941].
[75]
Tian, W.; Jiang, X.; Tamosiuniene, R.; Sung, Y.K.; Qian, J.; Dhillon, G.; Gera, L.; Farkas, L.; Rabinovitch, M.; Zamanian, R.T.; Inayathullah, M.; Fridlib, M.; Rajadas, J.; Peters-Golden, M.; Voelkel, N.F.; Nicolls, M.R. Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci. Transl. Med., 2013, 5(200)200ra117 [http://dx.doi.org/10.1126/scitranslmed.3006674]. [PMID: 23986401].
[76]
Tian, W.; Jiang, X.; Sung, Y.K.; Qian, J.; Yuan, K.; Nicolls, M.R. Leukotrienes in pulmonary arterial hypertension. Immunol. Res., 2014, 58(2-3), 387-393. [http://dx.doi.org/10.1007/s12026-014-8492-5]. [PMID: 24570092].
[77]
Ingegnoli, F.; Trabattoni, D.; Saresella, M.; Fantini, F.; Clerici, M. Distinct immune profiles characterize patients with diffuse or limited systemic sclerosis. Clin. Immunol., 2003, 108(1), 21-28. [http://dx.doi.org/10.1016/S1521-6616(03)00062-7]. [PMID: 12865067].
[78]
Sato, S.; Fujimoto, M.; Hasegawa, M.; Takehara, K. Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum., 2004, 50(6), 1918-1927. [http://dx.doi.org/10.1002/art.20274]. [PMID: 15188368].
[79]
Okano, Y.; Steen, V.D.; Medsger, T.A. Jr Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum., 1992, 35(1), 95-100. [http://dx.doi.org/10.1002/art.1780350114]. [PMID: 1731817].
[80]
Riemekasten, G.; Philippe, A.; Näther, M.; Slowinski, T.; Müller, D.N.; Heidecke, H.; Matucci-Cerinic, M.; Czirják, L.; Lukitsch, I.; Becker, M.; Kill, A.; van Laar, J.M.; Catar, R.; Luft, F.C.; Burmester, G.R.; Hegner, B.; Dragun, D. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann. Rheum. Dis., 2011, 70(3), 530-536. [http://dx.doi.org/10.1136/ard.2010.135772]. [PMID: 21081526].
[81]
Negi, V.S.; Tripathy, N.K.; Misra, R.; Nityanand, S. Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J. Rheumatol., 1998, 25(3), 462-466. [PMID: 9517764].
[82]
Bordron, A.; Dueymes, M.; Levy, Y.; Jamin, C.; Leroy, J.P.; Piette, J.C.; Shoenfeld, Y.; Youinou, P.Y. The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis. J. Clin. Invest., 1998, 101(10), 2029-2035. [http://dx.doi.org/10.1172/JCI2261]. [PMID: 9593758].
[83]
Tamby, M.C.; Humbert, M.; Guilpain, P.; Servettaz, A.; Dupin, N.; Christner, J.J.; Simonneau, G.; Fermanian, J.; Weill, B.; Guillevin, L.; Mouthon, L. Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur. Respir. J., 2006, 28(4), 799-807. [http://dx.doi.org/10.1183/09031936.06.00152705]. [PMID: 16774952].
[84]
Chizzolini, C.; Raschi, E.; Rezzonico, R.; Testoni, C.; Mallone, R.; Gabrielli, A.; Facchini, A.; Del Papa, N.; Borghi, M.O.; Dayer, J.M.; Meroni, P.L. Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum., 2002, 46(6), 1602-1613. [http://dx.doi.org/10.1002/art.10361]. [PMID: 12115192].
[85]
Terrier, B.; Tamby, M.C.; Camoin, L.; Guilpain, P.; Broussard, C.; Bussone, G.; Yaïci, A.; Hotellier, F.; Simonneau, G.; Guillevin, L.; Humbert, M.; Mouthon, L. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 2008, 177(10), 1128-1134. [http://dx.doi.org/10.1164/rccm.200707-1015OC]. [PMID: 18276943].
[86]
Huertas, A.; Perros, F.; Tu, L.; Cohen-Kaminsky, S.; Montani, D.; Dorfmüller, P.; Guignabert, C.; Humbert, M. Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay. Circulation, 2014, 129(12), 1332-1340. [http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004555]. [PMID: 24664216].
[87]
Chaisson, N.F.; Hassoun, P.M. Systemic sclerosis-associated pulmonary arterial hypertension. Chest, 2013, 144(4), 1346-1356. [http://dx.doi.org/10.1378/chest.12-2396]. [PMID: 24081346].
[89]
Cool, C.D.; Kennedy, D.; Voelkel, N.F.; Tuder, R.M. Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection. Hum. Pathol., 1997, 28(4), 434-442. [http://dx.doi.org/10.1016/S0046-8177(97)90032-0]. [PMID: 9104943].
[90]
Yao, J.S.; Zhai, W.; Fan, Y.; Lawton, M.T.; Barbaro, N.M.; Young, W.L.; Yang, G.Y. Interleukin-6 upregulates expression of KDR and stimulates proliferation of human cerebrovascular smooth muscle cells. J. Cereb. Blood Flow Metab., 2007, 27(3), 510-520. [http://dx.doi.org/10.1038/sj.jcbfm.9600365]. [PMID: 16820800].
[91]
Atkinson, C.; Stewart, S.; Upton, P.D.; Machado, R.; Thomson, J.R.; Trembath, R.C.; Morrell, N.W. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation, 2002, 105(14), 1672-1678. [http://dx.doi.org/10.1161/01.CIR.0000012754.72951.3D]. [PMID: 11940546].
[92]
Yeager, M.E.; Halley, G.R.; Golpon, H.A.; Voelkel, N.F.; Tuder, R.M. Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Circ. Res., 2001, 88(1), E2-E11. [http://dx.doi.org/10.1161/01.RES.88.1.e2]. [PMID: 11139485].
[93]
Brock, M.; Trenkmann, M.; Gay, R.E.; Michel, B.A.; Gay, S.; Fischler, M.; Ulrich, S.; Speich, R.; Huber, L.C. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ. Res., 2009, 104(10), 1184-1191. [http://dx.doi.org/10.1161/CIRCRESAHA.109.197491]. [PMID: 19390056].
[94]
Kugathasan, L.; Ray, J.B.; Deng, Y.; Rezaei, E.; Dumont, D.J.; Stewart, D.J. The angiopietin-1-Tie2 pathway prevents rather than promotes pulmonary arterial hypertension in transgenic mice. J. Exp. Med., 2009, 206(10), 2221-2234. [http://dx.doi.org/10.1084/jem.20090389]. [PMID: 19737862].
[95]
Imaizumi, T.; Yoshida, H.; Satoh, K. Regulation of CX3CL1/fractalkine expression in endothelial cells. J. Atheroscler. Thromb., 2004, 11(1), 15-21. [http://dx.doi.org/10.5551/jat.11.15]. [PMID: 15067194].
[96]
Semenza, G.L. Oxygen sensing, homeostasis, and disease. N. Engl. J. Med., 2011, 365(6), 537-547. [http://dx.doi.org/10.1056/NEJMra1011165]. [PMID: 21830968].
[97]
Archer, S.L.; Weir, E.K.; Wilkins, M.R. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation, 2010, 121(18), 2045-2066. [http://dx.doi.org/10.1161/CIRCULATIONAHA.108.847707]. [PMID: 20458021].
[98]
Michelakis, E.D.; McMurtry, M.S.; Wu, X.C.; Dyck, J.R.; Moudgil, R.; Hopkins, T.A.; Lopaschuk, G.D.; Puttagunta, L.; Waite, R.; Archer, S.L. Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels. Circulation, 2002, 105(2), 244-250. [http://dx.doi.org/10.1161/hc0202.101974]. [PMID: 11790708].
[99]
Bonnet, S.; Michelakis, E.D.; Porter, C.J.; Andrade-Navarro, M.A.; Thébaud, B.; Bonnet, S.; Haromy, A.; Harry, G.; Moudgil, R.; McMurtry, M.S.; Weir, E.K.; Archer, S.L. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation, 2006, 113(22), 2630-2641. [http://dx.doi.org/10.1161/CIRCULATIONAHA.105.609008]. [PMID: 16735674].
[100]
Piao, L.; Fang, Y.H.; Cadete, V.J.; Wietholt, C.; Urboniene, D.; Toth, P.T.; Marsboom, G.; Zhang, H.J.; Haber, I.; Rehman, J.; Lopaschuk, G.D.; Archer, S.L. The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle. J. Mol. Med. (Berl.), 2010, 88(1), 47-60. [http://dx.doi.org/10.1007/s00109-009-0524-6]. [PMID: 19949938].
[101]
Zhao, L.; Chen, C.N.; Hajji, N.; Oliver, E.; Cotroneo, E.; Wharton, J.; Wang, D.; Li, M.; McKinsey, T.A.; Stenmark, K.R.; Wilkins, M.R. Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid. Circulation, 2012, 126(4), 455-467. [http://dx.doi.org/10.1161/CIRCULATIONAHA.112.103176]. [PMID: 22711276].
[102]
Bertero, T.; Oldham, W.M.; Cottrill, K.A.; Pisano, S.; Vanderpool, R.R.; Yu, Q.; Zhao, J.; Tai, Y.; Tang, Y.; Zhang, Y.Y.; Rehman, S.; Sugahara, M.; Qi, Z.; Gorcsan, J., III; Vargas, S.O.; Saggar, R.; Saggar, R.; Wallace, W.D.; Ross, D.J.; Haley, K.J.; Waxman, A.B.; Parikh, V.N.; De Marco, T.; Hsue, P.Y.; Morris, A.; Simon, M.A.; Norris, K.A.; Gaggioli, C.; Loscalzo, J.; Fessel, J.; Chan, S.Y. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J. Clin. Invest., 2016, 126(9), 3313-3335. [http://dx.doi.org/10.1172/JCI86387]. [PMID: 27548520].
[103]
Dunham-Snary, K.J.; Wu, D.; Sykes, E.A.; Thakrar, A.; Parlow, L.R.G.; Mewburn, J.D.; Parlow, J.L.; Archer, S.L. Hypoxic pulmonary vasoconstriction: From molecular mechanisms to medicine. Chest, 2017, 151(1), 181-192. [http://dx.doi.org/10.1016/j.chest.2016.09.001]. [PMID: 27645688].
[104]
Ward, J.P.; McMurtry, I.F. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem. Curr. Opin. Pharmacol., 2009, 9(3), 287-296. [http://dx.doi.org/10.1016/j.coph.2009.02.006]. [PMID: 19297247].
[105]
Shadel, G.S.; Horvath, T.L. Mitochondrial ROS signaling in organismal homeostasis. Cell, 2015, 163(3), 560-569. [http://dx.doi.org/10.1016/j.cell.2015.10.001]. [PMID: 26496603].
[106]
Moudgil, R.; Michelakis, E.D.; Archer, S.L. Hypoxic pulmonary vasoconstriction. J. Appl. Physiol., 2005, 98(1), 390-403. [http://dx.doi.org/10.1152/japplphysiol.00733.2004]. [PMID: 15591309].
[107]
Archer, S.L.; Will, J.A.; Weir, E.K. Redox status in the control of pulmonary vascular tone. Herz, 1986, 11(3), 127-141. [PMID: 3017827].
[108]
Reeve, H.L.; Weir, E.K.; Nelson, D.P.; Peterson, D.A.; Archer, S.L. Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue. Exp. Physiol., 1995, 80(5), 825-834. [http://dx.doi.org/10.1113/expphysiol.1995.sp003890]. [PMID: 8546871].
[109]
Wang, G.L.; Jiang, B.H.; Semenza, G.L. Effect of altered redox states on expression and DNA-binding activity of hypoxia-inducible factor 1. Biochem. Biophys. Res. Commun., 1995, 212(2), 550-556. [http://dx.doi.org/10.1006/bbrc.1995.2005]. [PMID: 7626069].
[110]
Weir, E.K.; López-Barneo, J.; Buckler, K.J.; Archer, S.L. Acute oxygen-sensing mechanisms. N. Engl. J. Med., 2005, 353(19), 2042-2055. [http://dx.doi.org/10.1056/NEJMra050002]. [PMID: 16282179].
[111]
Bowers, R.; Cool, C.; Murphy, R.C.; Tuder, R.M.; Hopken, M.W.; Flores, S.C.; Voelkel, N.F. Oxidative stress in severe pulmonary hypertension. Am. J. Respir. Crit. Care Med., 2004, 169(6), 764-769. [http://dx.doi.org/10.1164/rccm.200301-147OC]. [PMID: 14701708].
[112]
Archer, S.L.; Marsboom, G.; Kim, G.H.; Zhang, H.J.; Toth, P.T.; Svensson, E.C.; Dyck, J.R.; Gomberg-Maitland, M.; Thébaud, B.; Husain, A.N.; Cipriani, N.; Rehman, J. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation, 2010, 121(24), 2661-2671. [http://dx.doi.org/10.1161/CIRCULATIONAHA.109.916098]. [PMID: 20529999].
[113]
Evans, A.M.; Hardie, D.G.; Peers, C.; Wyatt, C.N.; Viollet, B.; Kumar, P.; Dallas, M.L.; Ross, F.; Ikematsu, N.; Jordan, H.L.; Barr, B.L.; Rafferty, J.N.; Ogunbayo, O. Ion channel regulation by AMPK: the route of hypoxia-response coupling in thecarotid body and pulmonary artery. Ann. N. Y. Acad. Sci., 2009, 1177, 89-100. [http://dx.doi.org/10.1111/j.1749-6632.2009.05041.x]. [PMID: 19845611].
[114]
Moral-Sanz, J.; Mahmoud, A.D.; Ross, F.A.; Eldstrom, J.; Fedida, D.; Hardie, D.G.; Evans, A.M. AMP-activated protein kinase inhibits Kv 1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation. J. Physiol., 2016, 594(17), 4901-4915. [http://dx.doi.org/10.1113/JP272032]. [PMID: 27062501].
[115]
Lai, Y.C.; Tabima, D.M.; Dube, J.J.; Hughan, K.S.; Vanderpool, R.R.; Goncharov, D.A.; St. Croix, C.M.; Garcia-Ocaña, A.; Goncharova, E.A.; Tofovic, S.P.; Mora, A.L.; Gladwin, M.T. Sirt3-amp-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction. Circulation, 2016, 133(8), 717-731. [http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018935]. [PMID: 26813102].
[116]
Aramburu, J.; Yaffe, M.B.; López-Rodríguez, C.; Cantley, L.C.; Hogan, P.G.; Rao, A. Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A. Science, 1999, 285(5436), 2129-2133. [http://dx.doi.org/10.1126/science.285.5436.2129]. [PMID: 10497131].
[117]
Robinson, J.C.; Graham, B.B.; Rouault, T.C.; Tuder, R.M. The crossroads of iron with hypoxia and cellular metabolism. Implications in the pathobiology of pulmonary hypertension. Am. J. Respir. Cell Mol. Biol., 2014, 51(6), 721-729. [http://dx.doi.org/10.1165/rcmb.2014-0021TR]. [PMID: 24988529].
[118]
Ruiter, G.; Lankhorst, S.; Boonstra, A.; Postmus, P.E.; Zweegman, S.; Westerhof, N.; van der Laarse, W.J.; Vonk-Noordegraaf, A. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur. Respir. J., 2011, 37(6), 1386-1391. [http://dx.doi.org/10.1183/09031936.00100510]. [PMID: 20884742].
[119]
Smith, T.G.; Talbot, N.P.; Privat, C.; Rivera-Ch, M.; Nickol, A.H.; Ratcliffe, P.J.; Dorrington, K.L.; León-Velarde, F.; Robbins, P.A. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA, 2009, 302(13), 1444-1450. [http://dx.doi.org/10.1001/jama.2009.1404]. [PMID: 19809026].
[120]
Frise, M.C.; Cheng, H.Y.; Nickol, A.H.; Curtis, M.K.; Pollard, K.A.; Roberts, D.J.; Ratcliffe, P.J.; Dorrington, K.L.; Robbins, P.A. Clinical iron deficiency disturbs normal human responses to hypoxia. J. Clin. Invest., 2016, 126(6), 2139-2150. [http://dx.doi.org/10.1172/JCI85715]. [PMID: 27140401].
[121]
Ruiter, G.; Manders, E.; Happé, C.M.; Schalij, I.; Groepenhoff, H.; Howard, L.S.; Wilkins, M.R.; Bogaard, H.J.; Westerhof, N.; van der Laarse, W.J.; de Man, F.S.; Vonk-Noordegraaf, A. Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency. Pulm. Circ., 2015, 5(3), 466-472. [http://dx.doi.org/10.1086/682217]. [PMID: 26401247].
[122]
Ghosh, M.C.; Zhang, D.L.; Jeong, S.Y.; Kovtunovych, G.; Ollivierre-Wilson, H.; Noguchi, A.; Tu, T.; Senecal, T.; Robinson, G.; Crooks, D.R.; Tong, W.H.; Ramaswamy, K.; Singh, A.; Graham, B.B.; Tuder, R.M.; Yu, Z.X.; Eckhaus, M.; Lee, J.; Springer, D.A.; Rouault, T.A. Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2α. Cell Metab., 2013, 17(2), 271-281. [http://dx.doi.org/10.1016/j.cmet.2012.12.016]. [PMID: 23395173].
[123]
Ghosh, M.C.; Tong, W.H.; Zhang, D.; Ollivierre-Wilson, H.; Singh, A.; Krishna, M.C.; Mitchell, J.B.; Rouault, T.A. Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice. Proc. Natl. Acad. Sci. USA, 2008, 105(33), 12028-12033. [http://dx.doi.org/10.1073/pnas.0805361105]. [PMID: 18685102].
[124]
Zhao, L.; Oliver, E.; Maratou, K.; Atanur, S.S.; Dubois, O.D.; Cotroneo, E.; Chen, C.N.; Wang, L.; Arce, C.; Chabosseau, P.L.; Ponsa-Cobas, J.; Frid, M.G.; Moyon, B.; Webster, Z.; Aldashev, A.; Ferrer, J.; Rutter, G.A.; Stenmark, K.R.; Aitman, T.J.; Wilkins, M.R. The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia. Nature, 2015, 524(7565), 356-360. [http://dx.doi.org/10.1038/nature14620]. [PMID: 26258299].
[125]
Harvey, L.D.; Chan, S.Y. Emerging metabolic therapies in pulmonary arterial hypertension. J. Clin. Med., 2017, 6(4), 6. [http://dx.doi.org/10.3390/jcm6040043]. [PMID: 28375184].
[126]
Boucherat, O.; Vitry, G.; Trinh, I.; Paulin, R.; Provencher, S.; Bonnet, S. The cancer theory of pulmonary arterial hypertension. Pulm. Circ., 2017, 7(2), 285-299. [http://dx.doi.org/10.1177/2045893217701438]. [PMID: 28597757].
[127]
Hassoun, P.M.; Mouthon, L.; Barberà, J.A.; Eddahibi, S.; Flores, S.C.; Grimminger, F.; Jones, P.L.; Maitland, M.L.; Michelakis, E.D.; Morrell, N.W.; Newman, J.H.; Rabinovitch, M.; Schermuly, R.; Stenmark, K.R.; Voelkel, N.F.; Yuan, J.X.; Humbert, M. Inflammation, growth factors, and pulmonary vascular remodeling. J. Am. Coll. Cardiol., 2009, 54(1)(Suppl.), S10-S19. [http://dx.doi.org/10.1016/j.jacc.2009.04.006]. [PMID: 19555853].
[128]
Suzuki, Y.J.; Ibrahim, Y.F.; Shults, N.V. Apoptosis-based therapy to treat pulmonary arterial hypertension. J.f Rare Dis. Res. Treat., 2016, 1, 17-24.
[129]
Kim, S.Y.; Lee, J.H.; Huh, J.W.; Kim, H.J.; Park, M.K.; Ro, J.Y.; Oh, Y.M.; Lee, S.D.; Lee, Y.S. Bortezomib alleviates experimental pulmonary arterial hypertension. Am. J. Respir. Cell Mol. Biol., 2012, 47(5), 698-708. [http://dx.doi.org/10.1165/rcmb.2011-0331OC]. [PMID: 22842494].
[130]
Wang, X.; Ibrahim, Y.F.; Das, D.; Zungu-Edmondson, M.; Shults, N.V.; Suzuki, Y.J. Carfilzomib reverses pulmonary arterial hypertension. Cardiovasc. Res., 2016, 110(2), 188-199. [http://dx.doi.org/10.1093/cvr/cvw047]. [PMID: 26952044].
[131]
Cross, S.A.; Lyseng-Williamson, K.A. Imatinib: in relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukaemia. Drugs, 2007, 67(17), 2645-2654. [http://dx.doi.org/10.2165/00003495-200767170-00013]. [PMID: 18034597].
[132]
Hernández-Boluda, J.C.; Cervantes, F. Imatinib mesylate (Gleevec, Glivec): a new therapy for chronic myeloid leukemia and other malignancies. Drugs Today (Barc), 2002, 38(9), 601-613. [http://dx.doi.org/10.1358/dot.2002.38.9.696536]. [PMID: 12582448].
[133]
Knight, G.W.; McLellan, D. Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia. Br. J. Biomed. Sci., 2004, 61(2), 103-111. [http://dx.doi.org/10.1080/09674845.2004.11732653]. [PMID: 15250677].
[134]
Schermuly, R.T.; Dony, E.; Ghofrani, H.A.; Pullamsetti, S.; Savai, R.; Roth, M.; Sydykov, A.; Lai, Y.J.; Weissmann, N.; Seeger, W.; Grimminger, F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J. Clin. Invest., 2005, 115(10), 2811-2821. [http://dx.doi.org/10.1172/JCI24838]. [PMID: 16200212].
[135]
Nakamura, K.; Akagi, S.; Ogawa, A.; Kusano, K.F.; Matsubara, H.; Miura, D.; Fuke, S.; Nishii, N.; Nagase, S.; Kohno, K.; Morita, H.; Oto, T.; Yamanaka, R.; Otsuka, F.; Miura, A.; Yutani, C.; Ohe, T.; Ito, H. Pro-apoptotic effects of imatinib on PDGF-stimulated pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. Int. J. Cardiol., 2012, 159(2), 100-106. [http://dx.doi.org/10.1016/j.ijcard.2011.02.024]. [PMID: 21376411].
[136]
Speich, R.; Ulrich, S.; Domenighetti, G.; Huber, L.C.; Fischler, M.; Treder, U.; Breitenstein, A. Efficacy and safety of long-term imatinib therapy for pulmonary arterial hypertension. Resp. Int. Rev. Thor. Dis., 2015, 89, 515-524.
[137]
Hoeper, M.M.; Barst, R.J.; Bourge, R.C.; Feldman, J.; Frost, A.E.; Galié, N.; Gómez-Sánchez, M.A.; Grimminger, F.; Grünig, E.; Hassoun, P.M.; Morrell, N.W.; Peacock, A.J.; Satoh, T.; Simonneau, G.; Tapson, V.F.; Torres, F.; Lawrence, D.; Quinn, D.A.; Ghofrani, H.A. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation, 2013, 127(10), 1128-1138. [http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000765]. [PMID: 23403476].
[138]
Frost, A.E.; Barst, R.J.; Hoeper, M.M.; Chang, H.J.; Frantz, R.P.; Fukumoto, Y.; Galie, N.; Hassoun, P.M.; Klose, H.; Matsubara, H.; Morrell, N.W.; Peacock, A.J.; Pfeifer, M.; Simonneau, G.; Tapson, V.F.; Torres, F.; Dario Vizza, C.; Lawrence, D.; Yang, W.; Felser, J.M.; Quinn, D.A.; Ghofrani, H.A. Long-term safety and efficacy of imatinib in pulmonary arterial hypertension. J. Heart Lung Transplant., 2015, 34, 1366-1375.
[139]
Laplante, M.; Sabatini, D.M. mTOR signaling at a glance. J. Cell Sci., 2009, 122(Pt 20), 3589-3594. [http://dx.doi.org/10.1242/jcs.051011]. [PMID: 19812304].
[140]
Kudryashova, T.V.; Goncharov, D.A.; Pena, A.; Ihida-Stansbury, K.; DeLisser, H.; Kawut, S.M.; Goncharova, E.A. Profiling the role of mammalian target of rapamycin in the vascular smooth muscle metabolome in pulmonary arterial hypertension. Pulm. Circ., 2015, 5(4), 667-680. [http://dx.doi.org/10.1086/683810]. [PMID: 26697174].
[141]
Seyfarth, H.J.; Hammerschmidt, S.; Halank, M.; Neuhaus, P.; Wirtz, H.R. Everolimus in patients with severe pulmonary hypertension: a safety and efficacy pilot trial. Pulm. Circ., 2013, 3(3), 632-638. [http://dx.doi.org/10.1086/674311]. [PMID: 24618547].
[142]
Spiekerkoetter, E.; Tian, X.; Cai, J.; Hopper, R.K.; Sudheendra, D.; Li, C.G.; El-Bizri, N.; Sawada, H.; Haghighat, R.; Chan, R.; Haghighat, L.; de Jesus Perez, V.; Wang, L.; Reddy, S.; Zhao, M.; Bernstein, D.; Solow-Cordero, D.E.; Beachy, P.A.; Wandless, T.J.; Ten Dijke, P.; Rabinovitch, M. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J. Clin. Invest., 2013, 123(8), 3600-3613. [http://dx.doi.org/10.1172/JCI65592]. [PMID: 23867624].
[143]
Savai, R.; Al-Tamari, H.M.; Sedding, D.; Kojonazarov, B.; Muecke, C.; Teske, R.; Capecchi, M.R.; Weissmann, N.; Grimminger, F.; Seeger, W.; Schermuly, R.T.; Pullamsetti, S.S. Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat. Med., 2014, 20(11), 1289-1300. [http://dx.doi.org/10.1038/nm.3695]. [PMID: 25344740].
[144]
Yin, Y.; Wu, X.; Yang, Z.; Zhao, J.; Wang, X.; Zhang, Q.; Yuan, M.; Xie, L.; Liu, H.; He, Q. The potential efficacy of R8-modified paclitaxel-loaded liposomes on pulmonary arterial hypertension. Pharm. Res., 2013, 30(8), 2050-2062. [http://dx.doi.org/10.1007/s11095-013-1058-8]. [PMID: 23756757].
[145]
Ameri, P.; Bertero, E.; Meliota, G.; Cheli, M.; Canepa, M.; Brunelli, C.; Balbi, M. Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure. Heart Fail. Rev., 2016, 21(5), 539-547. [http://dx.doi.org/10.1007/s10741-016-9566-3]. [PMID: 27206576].
[146]
Provencher, S.; Herve, P.; Jais, X.; Lebrec, D.; Humbert, M.; Simonneau, G.; Sitbon, O. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology, 2006, 130(1), 120-126. [http://dx.doi.org/10.1053/j.gastro.2005.10.013]. [PMID: 16401475].
[147]
Zhou, L.; Zhang, J.; Jiang, X.M.; Xie, D.J.; Wang, J.S.; Li, L.; Li, B.; Wang, Z.M.; Rothman, A.M.K.; Lawrie, A.; Chen, S.L. Pulmonary artery denervation attenuates pulmonary arterial remodeling in dogs with pulmonary arterial hypertension induced by dehydrogenized monocrotaline. JACC Cardiovasc. Interv., 2015, 8(15), 2013-2023. [http://dx.doi.org/10.1016/j.jcin.2015.09.015]. [PMID: 26738673].
[148]
Rothman, A.M.; Arnold, N.D.; Chang, W.; Watson, O.; Swift, A.J.; Condliffe, R.; Elliot, C.A.; Kiely, D.G.; Suvarna, S.K.; Gunn, J.; Lawrie, A. Pulmonary artery denervation reduces pulmonary artery pressure and induces histological changes in an acute porcine model of pulmonary hypertension. Circ. Cardiovasc. Interv., 2015, 8(11)e002569 [http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.002569]. [PMID: 26553697].
[149]
Chen, S.L.; Zhang, F.F.; Xu, J.; Xie, D.J.; Zhou, L.; Nguyen, T.; Stone, G.W. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J. Am. Coll. Cardiol., 2013, 62(12), 1092-1100. [http://dx.doi.org/10.1016/j.jacc.2013.05.075]. [PMID: 23850902].
