Cellular and molecular pathobiology of pulmonary arterial hypertension

Journal of the American College of Cardiology

Volumn 43, Issue 12 SUPPL., 2004, Pages S13-S24

  Humbert, Marc ^a,k   Morrell, Nicholas W ^b   Archer, Stephen L ^c   Stenmark, Kurt R ^d   MacLean, Margaret R ^e   Lang, Irene M ^f   Christman, Brian W ^g   Weir, E Kenneth ^h   Eickelberg, Oliver ⁱ   Voelkel, Norbert F ^d   Rabinovitch, Marlene ^j  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF ALBERTA   (Canada)

^d UNIVERSITY OF COLORADO   (United States)

^e UNIVERSITY OF GLASGOW   (United Kingdom)

^f UNIVERSITY OF VIENNA   (Austria)

^g VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h VETERANS AFFAIRS MEDICAL CENTER   (United States)

ⁱ JUSTUS LIEBIG UNIVERSITY   (Germany)

^j STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k HÔPITAL ANTOINE BÉCLÈRE   (France)

more..

Author keywords

5 HT; 5 hydroxytryptamine; BMP; bone morphogenetic proteins; endothelin; ET; nitric oxide; NO; PAH; pulmonary arterial hypertension; TGF ; TGF R2; transforming growth factor beta; transforming growth factor beta type 2 receptor; VEGF

Indexed keywords

ANGIOPOIETIN 1; CHEMOKINE; CYTOKINE; ENDOTHELIN 1; NITRIC OXIDE; POTASSIUM CHANNEL; PROSTACYCLIN; SEROTONIN; TRANSFORMING GROWTH FACTOR BETA; VASOACTIVE INTESTINAL POLYPEPTIDE;

ANGIOGENESIS; APOPTOSIS; ARTERY WALL; CONFERENCE PAPER; CYTOPATHOLOGY; DISEASE ASSOCIATION; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; FIBROBLAST; GENETIC CORRELATION; HUMAN; INFLAMMATORY CELL; LUNG ARTERY; LUNG VASCULAR RESISTANCE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN INDUCTION; PULMONARY HYPERTENSION; SMOOTH MUSCLE FIBER; THROMBOCYTE; THROMBOSIS;

EID: 2942541475     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jacc.2004.02.029     Document Type: Conference Paper

References (61)

1. Voelkel N.F., Tuder R.M., Weir E.K. Pathophysiology of primary pulmonary hypertension. Rubin L., Rich S. Primary Pulmonary Hypertension. 1997;83-129 Marcel Dekker, New York, NY
2. Jeffery T.K., Morrell N.W. Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis. 45:2002;173-202
3. Stenmark K.R., Gerasimovskaya E., Nemenoff R.A., Das M. Hypoxic activation of adventitial fibroblasts Role in vascular remodeling. Chest. 122:2002;326S-334S
4. Davie N.J., Crossno J.T., Frid M.G., et al. Hypoxia-induced pulmonary artery advential remodeling and neovascularization Contribution of progenitor cells. Am J Physiol Lung Cell Mol Physiol. 286:2004;668-678
5. Cool C.D., Stewart J.S., Wehareha P., et al. Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth. Am J Pathol. 155:1999;411-419
6. Lee S.D., Shroyer K.R., Markham N.E., Cool C.D., Voelkel N.F., Tuder R.M. Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension. J Clin Invest. 101:1998;927-934
7. 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. 88:2001;e2-e11
8. Cool C.D., Rai P.R., Yeager M.E., et al. Expression of human herpesvirus-8 in primary pulmonary hypertension. N Engl J Med. 349:2003;1113-1122
9. Dorfmüller P., Perros F., Balabanian K., Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J. 22:2003;358-363
10. Balabanian K., Foussat A., Dorfmüller P., et al. CX (3) C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med. 165:2002;1419-1425
11. Hervé P., Humbert M., Sitbon O., et al. Pathobiology of pulmonary hypertension The role of platelets and thrombosis. Clin Chest Med. 22:2001;451-458
12. Christman B.W., McPherson C.D., Newman J.H., et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 327:1992;70-75
13. Tuder R.M., Cool C.D., Geraci M.W., 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
14. Giaid A., Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 333:1995;214-221
15. Michelakis E.D., Tymchak W., Noga M., et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation. 108:2003;2066-2069
16. Petkov V., Mosgoeller W., Ziesche R., et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 111:2003;1339-1346
17. Giaid A., Yanagisawa M., Langleben D., et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 328:1993;1732-1739
18. Archer S., Rich S. Primary pulmonary hypertension A vascular biology and translational research "work in progress." Circulation. 102:2000;2781-2791
19. + channel gene transcription in primary pulmonary hypertension. Lancet. 351:1998;726-727
20. Michelakis E.D., McMurtry M.S., Wu X.C., et al. 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. 105:2002;244-250
21. Geraci M.W., Moore M., Gesell T., et al. Gene expression patterns in the lungs of patients with primary pulmonary hypertension A gene microarray analysis. Circ Res. 88:2001;555-562
22. Weir E.K., Reeve H.L., Huang J.M.C., et al. Anorexic agents aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in rat pulmonary vascular smooth muscle and cause pulmonary vasoconstriction. Circulation. 94:1996;2216-2220
23. Hervé P., Launay J.M., Scrobohaci M.L., et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med. 99:1995;249-254
24. MacLean M.R., Hervé P., Eddahibi S., Adnot S. 5-Hydroxytryptamine and the pulmonary circulation Receptors, transporters and relevance to pulmonary arterial hypertension. Br J Pharmacol. 131:2000;161-168
25. Eddahibi S., Humbert M., Fadel E., et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest. 108:2001;1141-1150
26. Eddahibi S., Chaouat A., Morrell N., et al. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation. 108:2003;1839-1844
27. MacLean MR, Deuchar GA, Hicks MN, et al. Over-expression of the 5-hydroxytryptamine transporter gene: effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension. Circulation 2004. In press.
28. Marcos E., Adnot S., Pham M.H., et al. Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am J Respir Crit Care Med. 168:2003;487-493
29. Morecroft I., Heeley R.P., Prentice H.M., Kirk A., MacLean M.R. 5-Hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries Importance of the 5-ht1b receptor. Br J Pharmacol. 128:1999;730-734
30. Keegan A., Morecroft I., Smillie D., Hicks M.N., MacLean M.R. Contribution of the 5-HT (1B) receptor to hypoxia-induced pulmonary hypertension Converging evidence using 5-ht (1b)-receptor knockout mice and the 5-ht (1b/1d)-receptor antagonist gr127935. Circ Res. 89:2001;1231-1239
31. Launay J.M., Hervé P., Peoc'h K., et al. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med. 8:2002;1129-1135
32. Weir E.K., Reeve H.L., Peterson D.A., Michelakis E.D., Nelson D.P., Archer S.L. Pulmonary vasoconstriction, oxygen sensing, and the role of ion channels Thomas a. neff lecture. Chest. 114:1998;17S-22S
33. Massague J., Chen Y.G. Controlling TGF-beta signaling. Genes Dev. 14:2000;627-644
34. Shi Y., Massague J. Mechanisms of TGF-beta signaling from cell membrane to nucleus. Cell. 113:2003;685-700
35. Lane K.B., Machado R.D., Pauciulo M.W., et al. Heterozygous germline mutations in a TGF-β receptor, BMPR2, are the cause of familial primary pulmonary hypertension. Nat Genet. 26:2000;81-84
36. Deng Z., Morse J.H., Slager S.L., et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet. 67:2000;737-744
37. Thomson J.R., Machado R.D., Pauciulo M.W., et al. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-β family. J Med Genet. 37:2000;741-745
38. Trembath R., Thomson J.R., Machado R.D., et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 345:2001;325-334
39. Chaouat A, Coulet F, Favre C, et al. Endoglin germline mutation in a patient with hereditary hemorrhagic telangiectasia and dexfenfluramine- associated pulmonary arterial hypertension. Thorax 2004;59:446-8.
40. Rudarakanchana N., Flanagan J.A., Chen H., et al. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet. 11:2002;1517-1525
41. Beppu H., Kawabata M., Hamamoto T., et al. BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol. 221:2000;249-258
42. Atkinson C., Stewart S., Upton P.D., et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation. 105:2002;1672-1678
43. Du L., Sullivan C.C., Chu D., et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med. 348:2003;500-509
44. Morrell N.W., Yang X., Upton P., et al. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-β1 and bone morphogenetic proteins. Circulation. 104:2001;790-795
45. Machado R.D., Pauciulo M.W., Thomson J.R., et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet. 68:2001;92-102
46. Botney M.D., Bahadori L., Gold L.I. Vascular remodeling in primary pulmonary hypertension Potential role for transforming growth factor-β Am J Pathol. 144:1994;286-295
47. Markewitz B.A., Farrukh I.S., Chen Y., Li Y., Michael J.R. Regulation of endothelin-1 synthesis in human pulmonary arterial smooth muscle cells Effects of transforming growth factor-β and hypoxia. Cardiovasc Res. 49:2001;200-206
48. Kucich U., Rosenbloom J.C., Herrick D.J., et al. Signaling events required for transforming growth factor-β stimulation of connective tissue growth factor expression by cultured human lung fibroblasts. Arch Biochem Biophys. 395:2001;103-112
49. Tuder R.M., Chacon M., Alger L., et al. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension Evidence for a process of disordered angiogenesis. J Pathol. 195:2001;367-374
50. Wanstall J.C., Gambino A., Jeffery T.K., et al. Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension. Cardiovasc Res. 55:2002;361-368
51. Campbell A.I., Zhao Y., Sandhu R., Stewart D.J. Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension. Circulation. 104:2001;2242-2248
52. Hirose S., Hosoda Y., Furuya S., Otsuki T., Ikeda E. Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension. Pathol Int. 50:2000;472-479
53. Taraseviciene-Stewart T., Kasahara Y., Alger L., 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
54. Sullivan C.C., Du L., Chu D., et al. Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway. Proc Natl Acad Sci U S A. 100:2003;12331-12336
55. Zhao Y.D., Campbell A.I.M., Robb M., Ng D., Stewart D.J. Protective role of angiopoietin-1 in experimental pulmonary hypertension. Circ Res. 92:2003;984-991
56. Rudge J.S., Thurston G., Yancopoulos G.D. Angiopoietin-1 and pulmonary hypertension Cause or cure? Circ Res. 92:2003;947-949
57. Rabinovitch M. Elastase and the pathobiology of unexplained pulmonary hypertension. Chest. 114:1998;213S-224S
58. Cowan K.N., Jones P.L., Rabinovitch M. Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease. J Clin Invest. 105:2000;21-34
59. Cowan K.N., Heilbut A., Humpl T., Lam C., Ito S., Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med. 6:2000;698-702
60. Wigle D.A., Thompson K.E., Yablonsky S., et al. AML1-like transcription factor induces serine elastase activity in ovine pulmonary artery smooth muscle cells. Circ Res. 10:1998;252-263
61. Mitani Y., Zaidi S.H., Dufourcq P., Thompson K., Rabinovitch M. Nitric oxide reduces vascular smooth muscle cell elastase activity through cGMP-mediated suppression of ERK phosphorylation and AML1B nuclear partitioning. FASEB J. 14:2000;805-814