Role of apoptosis in pulmonary hypertension: From experimental models to clinical trials

Pharmacology and Therapeutics

Volumn 126, Issue 1, 2010, Pages 1-8

  Jurasz, Paul ^a   Courtman, David ^a,b   Babaie, Saeid ^a   Stewart, Duncan J ^a,b,c,d,e  

^a ST MICHAEL'S HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c McLaughlin Centre for Molecular Medicine   (Canada)

^d OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^e UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Apoptosis; Bone morphogenetic protein receptor 2 (Bmpr2); Pulmonary arterial hypertension (PAH); Vascular remodeling

Indexed keywords

ADENOVIRUS VECTOR; ADRENOMEDULLIN; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ILOPROST; PROSTACYCLIN DERIVATIVE; PROSTACYCLIN SYNTHASE; SILDENAFIL; VASODILATOR AGENT;

APOPTOSIS; CELL BASED GENE THERAPY; CELL PROLIFERATION; CELL REGENERATION; CLINICAL FEATURE; CLINICAL STUDY; CLINICAL TRIAL; DISEASE PREDISPOSITION; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENDOTHELIUM INJURY; EXPERIMENTAL MODEL; HUMAN; HYPERTROPHY; LIPOSOMAL GENE DELIVERY SYSTEM; LUNG CAPILLARY; LUNG CIRCULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PULMONARY ARTERY OCCLUSION; PULMONARY HYPERTENSION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; VASCULAR SURGERY; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; APOPTOSIS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; HUMANS; HYPERTENSION, PULMONARY; LUNG; MUTATION; NITRIC OXIDE SYNTHASE; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION;

EID: 77649337086     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2009.12.006     Document Type: Review

References (74)

1. Ambrosini G., Adida C., and Altieri D.C. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3 (1997) 917-921
2. Alavi A., Hood J.D., Frausto R., Stupack D.G., and Cheresh D.A. Role of Raf in vascular protection from distinct apoptotic stimuli. Science 301 (2003) 94-96
3. Archer S.L., and Michelakis E.D. An evidence-based approach to the management of pulmonary arterial hypertension. Curr Opin Cardiol 21 (2006) 385-392
4. Arcot S.S., Lipke D.W., Gillespie M.N., and Olsen J.W. Alterations of growth factor transcripts in rat lungs during development of monocrotaline-induced pulmonary hypertension. Biochem Pharma 46 (1993) 1086-1091
5. Atkinson C., Stewart S., Upton P.D., Machado R., Thomson J.R., Trembath R.C., et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105 (2002) 1672-1678
6. Budhiraja R., Tuder R.M., and Hassoun P.M. Endothelial dysfunction in pulmonary hypertension. Circulation 109 (2004) 159-165
7. Campbell A.I.M., Kuliszewski M.A., and Stewart D.J. Cell-based gene transfer to the pulmonary vasculature: endothelial nitric oxide synthase overexpression inhibits monocrotaline-induced pulmonary hypertension. Am J Resp Cell Mol Biol 21 (1999) 567-575
8. Campbell A.I.M., Zhao Y., Sandhu R., and Stewart D.J. Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension. Circulation 104 (2001) 2242-2248
9. Christman B.W., McPherson C.D., Newman J.H., King G.A., Bernard G.R., Groves B.M., et al. An imbalance between excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Eng J Med 237 (1992) 70-75
10. Cowan K.N., Heilbut A., Humpl T., Lam C., Ito S., and Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Genet 6 (2000) 698-702
11. Czer G.T., Marsh J., Konopka R., and Moser K.M. Low-dose PGI2 prevents monocrotaline-induced thromboxane production and lung injury. J Appl Physiol 60 (1986) 464-471
12. Gaine S. Pulmonary hypertension. J Am Med Assoc 284 (2000) 3160-3168
13. Giaid A., and Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary arterial hypertension. N Engl J Med 333 (1995) 214-221
14. Giaid A., Yanagisawa M., Langleben D., Michel R.P., Levy R., Shennib H., et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 328 (1993) 1732-1739
15. Gillespie M.N., Olson J.W., Reinsel C.N., O'Connor W.N., and Altiere R.J. Vascular hyperresponsiveness in perfused lungs from moncrotaline treated rats. Am J Physiol 251 (1986) H109-H114
16. Herve P., Launay J.M., Scrobohaci M.L., Brenot F., Simonneau G., Petitpretz P., et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med 99 (1995) 249-254
17. Hilliker K.S., and Roth R.A. Increased vascular responsiveness in lungs of rats with pulmonary hypertension induced my monocrotaline pyrrole. Am Rev Resp Dis 131 (1985) 46-50
18. Hilliker K.S., Bell T.G., and Roth R.A. Monocrotaline pyrrole-induced pulmonary hypertension in fawn-hooded rats with platelet storage pool deficiency: 5-hydroxytryptamine uptake by isolated, perfused lungs. Thromb Haemost 50 (1983) 844-847
19. Ito K., Hayashi K., Nakashima T., and Murakami T. Alteration of fate of vasoactive autacoids in pulmonary circulation following monocrotaline-induced lung vascular injury in rats. Br J Pharmacol 94 (1988) 1167-1174
20. Ito T., Okada T., Mimuro J., Miyashita H., Uchibori R., Urabe M., et al. Adenoassociated virus mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats. Hypertension 50 (2007) 531-536
21. Ito T., Okada T., Miyashita H., Nomoto T., Nonaka-Sarukawa M., Uchibori R., et al. Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension. Circ Res 101 (2007) 734-741
22. Janakidevi K., Fisher M.A., Del Vecchio P.J., Tiruppathi C., Figge J., and Malik A.B. Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Physiol 263 (1992) C1295-C1301
23. Johnson S.R., Granton J.T., and Mehta S. Thrombotic arteriopathy and anticoagulation in pulmonary hypertension. Chest 130 (2006) 545-552
24. Jones P.L., and Rabinovitch M. Tenascin-C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation. Circ Res 79 (1996) 1131-1142
25. Kanai Y., Hori S., Tanaka T., Yasuoka M., Watanabe K., Aikawa N., et al. Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats. Cardiovasc Res 27 (1993) 1619-1623
26. Kanki-Horimoto S., Horimoto H., Mieno S., Kishida K., Watanabe F., Furuya E., et al. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension. Circulation 114 (2006) I-181-I-185
27. Kido M., Hirose T., Tanaka K., Kurosumi T., and Shoyama Y. Increased alveolar-capillary membrane permeability by monocrotaline. Jpn J Med 20 (1981) 170-179
28. Lane K.B., Machado R.D., Pauciulo M.W., Thomas J.R., Phillips III J.A., Loyd J.E., et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26 (2000) 81-84
29. Levy M., Maurey C., Celermajer D.S., Vouhe P.R., Danel C., and Bonnet D. Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease. J Am Coll Cardiol 49 (2007) 803-810
30. Liu L., Liu H., Visner G., and Fletcher B.S. Sleeping beauty-mediated eNOS gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J 20 (2006) E2068-E2076
31. Loyd J.E., Primm R.K., and Newman J.H. Familial primary pulmonary hypertension: clinical patterns. Am Rev Resp Dis 129 (1984) 194-197
32. Machado R.D., Pauciulo M.W., Thomson J.R., Lane K.B., Morgan N.V., Wheeler L., et al. BMPR2 Haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68 (2001) 92-102
33. Mason N.A., Springall D.R., Burke M., Pollock J., Mikhail G., Yacoub M.H., et al. High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension. J Pathol 185 (1998) 313-318
34. Masri F.A., Xu W., Comhair S.A.A., Asosingh K., Koo M., Vasanji A., et al. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 293 (2007) L548-L554
35. Mathew R., Zeballos G.A., Tun H., and Gewitz M.H. Role of nitric oxide and endothelin-1 in monocrotaline-induced pulmonary hypertension in rats. Cardiovasc Res 30 (1995) 739-746
36. McMurtry M.S., Bonnet S., Wu X., Dyck J.R.B., Haromy A., Hashimoto K., et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle apoptosis. Circ Res 95 (2004) 830-840
37. McMurtry M.S., Archer S.L., Altieri D.C., Bonnet S., Haromy A., Harry G., et al. Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 115 (2005) 1479-1491
38. McMurtry M.S., Bonnet S., Michelakis E.D., Bonnet S., Haromy A., and Archer S.L. Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: the rapamcyin-atorvastatin-simvastatin study. AJP Lung Cell Mol Physiol 293 (2007) L933-L940
39. Merklinger S.L., Jones P.L., Martinez E.C., and Rabinovitch M. Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 112 (2005) 423-431
40. Molteni A., Ward W.F., Ts'ao C.H., Port C.D., and Solliday N.H. Monocrotaline-induced pulmonary endothelial dysfunction in rats. Proc Soc Exp Biol Med 176 (1984) 88-94
41. Morbidelli L., Orlando C., Maggi C.A., Ledda F., and Ziche M. Proliferation and migration of endothelial cells is promoted by endothelins via activation of ETB receptors. Am J Physiol 269 (1996) H686-695
42. Morbidelli L., Chang C.H., Douglas J.G., Granger H.J., Ledda F., and Ziche M. Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol 270 (1996) H411-415
43. Morty R.E., Nejman B., Kwapiszewska G., Hecker M., Zakrzewicz A., Kouri F.M., et al. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary hypertension. Arteriosceler Thromb Vasc Biol 27 (2007) 1072-1078
44. Nagaya N., Yokoyama C., Kyotani S., Shimonishi M., Morishita R., Uematsu M., et al. Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats. Circ Res 102 (2000) 2005-2010
45. Nagaya N., Kangawa K., Kanda M., Uematsu M., Horio T., Fukuyama N., et al. Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells. Circulation 108 (2003) 889-895
46. Nana-Sinkam S.P., Lee J.D., Sotto-Santiago S., Stearman R.S., Keith R.L., Choudhury Q., et al. Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke. Am J Respir Crit Care Med 175 (2007) 676-685
47. Nishimura T., Vaszar L.T., Faul J.L., Zhao G., Berry J.G., Shi L., et al. Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells. Circulation 108 (2003) 1640-1645
48. Partovian C., Adnot S., Eddahibi S., Teiger E., Lavame M., Dreyfus P., et al. Heart and lung VEGF mRNA expression in rats with monocrotaline- or hypoxia induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 275 (1998) 1948-1956
49. Partovian C., Adnot S., Raffestin B., Louzier V., Levame M., Mavier I.M., et al. Am J Respir Cell Mol Biol 23 (2000) 762-771
50. Rosenberg H.C., and Rabinovitch M. Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension. Am J Physiol 255 (1988) H1484-H1491
51. Sakao S., Taraseviciene-Stewart L., Lee J.D., Wood K., Cool C.D., and Voelkel N.F. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cell. FASEB J 19 (2005) 1178-1180
52. Southwood M., Jeffery T.K., Yang X., Upton P.D., Hall S.M., Atkinson C., et al. J Pathol 214 (2008) 85-95
53. Stenmark K.R., Morganroth M.L., Remigio L.K., Voelkel N.F., Murphy R.C., Henson P.M., et al. Alveolar inflammation and arachidonate metabolism in monocrotaline-induced pulmonary hypertension. Am J Physiol 248 (1985) H859-H866
54. Stewart D.J., Levy R.D., Cernacek P., and Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease?. Ann Intern Med 114 (1991) 464-469
55. Sugita T., Stenmark K.R., Wagner Jr. W.W., Henson P.M., Henson J.E., Hyers T.M., et al. Abnormal alveolar cells in monocrotaline induced pulmonary hypertension. Exp Lung Res 5 (1983) 201-215
56. Szczeklik J., Dubiel J.S., Mysik M., Pyzik Z., Krol R., and Horzela T. Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension. Br Heart J 40 (1978) 1397-1401
57. Takahashi H., Goto N., Kojima Y., Tsuda Y., Morio Y., Muramatsu M., et al. Down-regulation of type II bone morphogenetic protein receptor in hypoxic hypertension. Am J Physiol Lung Cell Mol Physiol 290 (2005) L450-L458
58. Taraseviciene-Stewart L., Kasahara Y., Alger L., Hirth P., McMahon G., Waltenberger J., et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15 (2001) 427-438
59. Teichert-Kuliszewska K., Kutryk M.J.B., Kuliszewski M.A., Karoubi G., Courtman D.W., Zucco L., et al. Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial survival. Implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension. Circ Res 98 (2006) 209-217
60. Thomas H.C., Lame M.W., Dunston S.K., Segall H.J., and Wilson D.W. Monocrotaline pyrrole induces apoptosis in pulmonary artery endothelial cells. Toxicol Appl Pharmacol 151 (1998) 236-244
61. Thomson J.R., Machado R.D., Pauciulo M.W., Morgan N.V., Humbert M., Elliott G.C., et al. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. J Med Genet 37 (2000) 741-745
62. Todorovich-Hunter L., Johnson D.J., Ranger P., Keeley F.W., and Rabinovitch M. Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline. A biochemical and ultrastructural study. Lab Invest 58 (1988) 184-195
63. Tuder R.M., Cool C.D., Geraci M.W., Wang J., Abman S.H., Wright L., et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159 (1999) 1925-1932
64. Tuder R.M., Marecki J.C., Richter A., Fijalkowska I., and Flores S. Pathology of pulmonary hypertension. Clin Chest Med 28 (2007) 23-42
65. Wagner J.G., Petry T.W., and Roth R.A. Characterization of monocrotaline pyrrole-induced DNA-cross linking in pulmonary endothelium. Am J Physiol 262 (1992) L740-747
66. Wang X.X., Zhang F.R., Shang Y.P., Zhu J.H., Xie X.D., Tao Q.M., et al. Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardio 49 (2007) 1566-1571
67. Wilson D.W., Lame M.W., Dunston S.K., and Segall H.J. DNA damage cell checkpoint activities are altered in monocrotaline pyrrole-induced cell cycle arrest in human pulmonary artery endothelial cells. Toxicol Appl Pharmacol 166 (2000) 69-80
68. Zakrzewicz A., Kouri F.M., Nejman B., Kwapiszewska G., Hecker H., Sandu R., et al. The transforming growth factor-b/Smad2, 3 signaling axis is impaired in experimental pulmonary hypertension. Eur Respir J 29 (2007) 1094-1104
69. Zhang S., Fantozzi I., Tigno D.D., Yi E.S., Platoshyn O., Thistlethwaite P.A., et al. Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 285 (2003) L740-L754
70. Zhao Y.D., Campbell A.I.M., Robb M., Ng D., and Stewart D.J. Protective role of angiopoietin-1 in experimental pulmonary hypertension. Circ Res 92 (2003) 984-991
71. Zhao Y.D., Courtman D.W., Deng Y., Kugathasan L., Zhang Q., and Stewart D.J. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-drived endothelial-like progenitor cells: Efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 96 (2005) 442-450
72. Zhao Y.D., Courtman D.W., Ng D.S., Robb M.J., Deng Y.P., Trogadis J., et al. Microvascular regeneration in established pulmonary hypertension by angiogenic gene transfer. Am J Respir Cell Mol Biol 35 (2006) 182-189
73. Zhu B., Strada S., and Stevens T. Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 289 (2005) L196-L206
74. Ziche M., Morbidelli L., Choudhuri R., Zhang H.T., Donnini S., Granger H.J., et al. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99 (1997) 2625-2634