Endothelial Progenitor Cells and Pulmonary Arterial Hypertension

Heart Lung and Circulation

Volumn 23, Issue 7, 2014, Pages 595-601

  Chen, Haiying ^a   Strappe, Padraig ^b   Chen, Shuangfeng ^a   Wang, Le Xin ^a,b  

^a LIAOCHENG PEOPLE'S HOSPITAL   (China)

^b CHARLES STURT UNIVERSITY   (Australia)

Author keywords

Cell therapy; Endothelial progenitor cells (EPCs); Pulmonary arterial hypertension (PAH); Pulmonary disease; Vascular remodelling

Indexed keywords

CD133 ANTIGEN; CD34 ANTIGEN; CILOSTAZOL; ENDOTHELIN RECEPTOR ANTAGONIST; FASUDIL; PHOSPHODIESTERASE V INHIBITOR; PROSTAGLANDIN; RIOCIGUAT; SELEXIPAG; SILDENAFIL;

ANGIOGENESIS; CLINICAL FEATURE; DISEASE ASSOCIATION; DRUG MECHANISM; ENDOTHELIAL PROGENITOR CELL; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PULMONARY HYPERTENSION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; TISSUE REGENERATION; ENDOTHELIUM CELL; METABOLISM; PATHOLOGY; STEM CELL; VASCULAR REMODELING;

ENDOTHELIAL CELLS; HUMANS; HYPERTENSION, PULMONARY; STEM CELL TRANSPLANTATION; STEM CELLS; VASCULAR REMODELING;

EID: 84902074071     PISSN: 14439506     EISSN: 14442892     Source Type: Journal    
DOI: 10.1016/j.hlc.2014.02.007     Document Type: Review

References (98)

1. Mathew R. Pulmonary hypertension: current therapy and future prospects. Cardiovasc Hematol Agents Med Chem 2011, 9(3):165-182.
2. Launay J.M., Herve P., Callebert J., Mallat Z., Collet C., Doly S., et al. Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension. Blood 2012, 119(7):1772-1780.
3. Farkas L., Kolb M. Vascular repair and regeneration as a therapeutic target for pulmonary arterial hypertension. Respiration 2013, 85(5):355-364.
4. Pugh M.E., Hemnes A.R., Robbins I.M. Combination therapy in pulmonary arterial hypertension. Clin Chest Med 2013, 34(4):841-855.
5. Mirsky R., Jahn S., Koskenvuo J.W., Sievers R.E., Yim S.M., Ritner C., et al. Treatment of pulmonary arterial hypertension with circulating angiogenic cells. Am J Physiol Lung Cell Mol Physiol 2011, 301(1):L12-L19.
6. Toshner M., Morrell N.W. Endothelial progenitor cells in pulmonary hypertension - dawn of cell-based therapy?. Int J Clin Pract Suppl 2010, (165):7-12.
7. Diller G.P., Thum T., Wilkins M.R., Wharton J. Endothelial progenitor cells in pulmonary arterial hypertension. Trends Cardiovasc Med 2010, 20(1):22-29.
8. Yamamura A., Yamamura H., Yuan J.X. Enhanced Ca(2+)-sensing Receptor Function in Pulmonary Hypertension. Yakugaku Zasshi 2013, 133(12):1351-1359.
9. Sharma S., Sun X., Kumar S., Rafikov R., Aramburo A., Kalkan G., et al. Preserving mitochondrial function prevents the proteasomal degradation of GTP cyclohydrolase I. Free Radic Biol Med 2012, 53(2):216-229.
10. Enache I., Charles A.L., Bouitbir J., Favret F., Zoll J., Metzger D., et al. Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension. Mol Cell Biochem 2013, 373(1-2):161-170.
11. Kherbeck N., Tamby M.C., Bussone G., Dib H., Perros F., Humbert M., et al. The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension. Clin Rev Allergy Immunol 2013, 44(1):31-38.
12. Fessel J.P., Flynn C.R., Robinson L.J., Penner N.L., Gladson S., Kang C., et al. Hyperoxia Synergizes with Mutant BMPR2 to Cause Metabolic Stress, Oxidant Injury, and Pulmonary Hypertension. Am J Respir Cell Mol Biol 2013.
13. Chiong M., Morales P., Torres G., Gutierrez T., Garcia L., Ibacache M., et al. Influence of glucose metabolism on vascular smooth muscle cell proliferation. Vasa 2013, 42(1):8-16.
14. Cottrill K.A., Chan S.Y. Metabolic dysfunction in pulmonary hypertension: the expanding relevance of the Warburg effect. Eur J Clin Invest 2013.
15. Ghatnekar A., Chrobak I., Reese C., Stawski L., Seta F., Wirrig E., et al. Endothelial GATA-6 Deficiency Promotes Pulmonary Arterial Hypertension. Am J Pathol 2013, 182(6):2391-2406.
16. Grant J.S., White K., Maclean M.R., Baker A.H. MicroRNAs in pulmonary arterial remodeling. Cell Mol Life Sci 2013.
17. Drake K.M., Zygmunt D., Mavrakis L., Harbor P., Wang L., Comhair S.A., et al. Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. Am J Respir Crit Care Med 2011, 184(12):1400-1408.
18. Freund-Michel V., Guibert C., Dubois M., Courtois A., Marthan R., Savineau J.P., et al. Reactive oxygen species as therapeutic targets in pulmonary hypertension. Ther Adv Respir Dis 2013, 7(3):175-200.
19. Gosemann J.H., Friedmacher F., Hunziker M., Alvarez L., Corcionivoschi N., Puri P. Increased activation of NADPH oxidase 4 in the pulmonary vasculature in experimental diaphragmatic hernia. Pediatr Surg Int 2013, 29(1):3-8.
20. Dorfmuller P., Chaumais M.C., Giannakouli M., Durand-Gasselin I., Raymond N., Fadel E., et al. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension. Respir Res 2011, 12:119.
21. Demarco V.G., Whaley-Connell A.T., Sowers J.R., Habibi J., Dellsperger K.C. Contribution of oxidative stress to pulmonary arterial hypertension. World J Cardiol 2010, 2(10):316-324.
22. Wilkins M.R. Pulmonary hypertension: the science behind the disease spectrum. Eur Respir Rev 2012, 21(123):19-26.
23. Qiao L., Xie L., Shi K., Zhou T., Hua Y., Liu H. Notch signaling change in pulmonary vascular remodeling in rats with pulmonary hypertension and its implication for therapeutic intervention. PLoS One 2012, 7(12):e51514.
24. Delaney C., Gien J., Roe G., Isenberg N., Kailey J., Abman S.H. Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol 2013, 304(12):L894-L901.
25. Farha S., Sharp J., Asosingh K., Park M., Comhair S.A., Tang W.H., et al. Mast cell number, phenotype, and function in human pulmonary arterial hypertension. Pulm Circ 2012, 2(2):220-228.
26. Ichimori H., Kogaki S., Takahashi K., Ishida H., Narita J., Nawa N., et al. Drastic Shift From Positive to Negative Estrogen Effect on Bone Morphogenetic Protein Signaling in Pulmonary Arterial Endothelial Cells Under Hypoxia. Circ J 2013.
27. Han C., Hong K.H., Kim Y.H., Kim M.J., Song C., Kim S.J., et al. SMAD1 deficiency in either endothelial or smooth muscle cells can predispose mice to pulmonary hypertension. Hypertension 2013, 61(5):1044-1052.
28. Gangopahyay A., Oran M., Bauer E.M., Wertz J.W., Comhair S.A., Erzurum S.C., et al. Bone morphogenetic protein receptor II is a novel mediator of endothelial nitric-oxide synthase activation. J Biol Chem 2011, 286(38):33134-33140.
29. Burton V.J., Ciuclan L.I., Holmes A.M., Rodman D.M., Walker C., Budd D.C. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood 2011, 117(1):333-341.
30. Gonzalez-Nunez M., Munoz-Felix J.M., Lopez-Novoa J.M. The ALK-1/Smad1 pathway in cardiovascular physiopathology. A new target for therapy?. Biochim Biophys Acta 2013, 1832(10):1492-1510.
31. Alan B., Nalbantgil S. Genetic, cellular and molecular mechanisms of pulmonary arterial hypertension. Anadolu Kardiyol Derg 2010, 10(Suppl 1):9-13.
32. Yeager M.E., Frid M.G., Stenmark K.R. Progenitor cells in pulmonary vascular remodeling. Pulm Circ 2011, 1(1):3-16.
33. Dickinson M.G., Bartelds B., Borgdorff M.A., Berger R.M. The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models. Am J Physiol Lung Cell Mol Physiol 2013, 305(1):L1-L14.
34. Schober A., Zernecke A. Chemokines in vascular remodeling. Thromb Haemost 2007, 97(5):730-737.
35. Marsboom G., Toth P.T., Ryan J.J., Hong Z., Wu X., Fang Y.H., et al. Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res 2012, 110(11):1484-1497.
36. Jurasz P., Courtman D., Babaie S., Stewart D.J. Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials. Pharmacol Ther 2010, 126(1):1-8.
37. Morrell N.W., Adnot S., Archer S.L., Dupuis J., Jones P.L., MacLean M.R., et al. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol 2009, 54(1 Suppl):S20-S31.
38. Schermuly R.T., Ghofrani H.A., Wilkins M.R., Grimminger F. Mechanisms of disease: pulmonary arterial hypertension. Nat Rev Cardiol 2011, 8(8):443-455.
39. Fijalkowska I., Xu W., Comhair S.A., Janocha A.J., Mavrakis L.A., Krishnamachary B., et al. Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol 2010, 176(3):1130-1138.
40. Kim Y.M., Barnes E.A., Alvira C.M., Ying L., Reddy S., Cornfield D.N. Hypoxia-inducible factor-1alpha in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation. Circ Res 2013, 112(9):1230-1233.
41. Mojiri A., Nakhaii-Nejad M., Phan W.L., Kulak S., Radziwon-Balicka A., Jurasz P., et al. Hypoxia results in upregulation and de novo activation of von Willebrand factor expression in lung endothelial cells. Arterioscler Thromb Vasc Biol 2013, 33(6):1329-1338.
42. Farha S., Asosingh K., Xu W., Sharp J., George D., Comhair S., et al. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities. Blood 2011, 117(13):3485-3493.
43. Duong H.T., Erzurum S.C., Asosingh K. Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation. Angiogenesis 2011, 14(4):411-422.
44. Schechter T., Leucht S., Bouffet E., Cutz E., Gassas A., Huang A., et al. Pulmonary hypertensive vasculopathy following tandem autologous transplants in pediatric patients with CNS tumors. Biol Blood Marrow Transplant 2012.
45. Smadja D.M., Mauge L., Sanchez O., Silvestre J.S., Guerin C., Godier A., et al. Distinct patterns of circulating endothelial cells in pulmonary hypertension. Eur Respir J 2010, 36(6):1284-1293.
46. Junhui Z., Xingxiang W., Guosheng F., Yunpeng S., Furong Z., Junzhu C. Reduced number and activity of circulating endothelial progenitor cells in patients with idiopathic pulmonary arterial hypertension. Respir Med 2008, 102(7):1073-1079.
47. Anjum F., Lazar J., Zein J., Jamaleddine G., Demetis S., Wadgaonkar R. Characterization of altered patterns of endothelial progenitor cells in sickle cell disease related pulmonary arterial hypertension. Pulm Circ 2012, 2(1):54-60.
48. Ghofrani H., Grimminger F. Soluble guanylate cyclase stimulation: an emerging option in pulmonary hypertension therapy. European Respiratory Review 2009, 18(111):35-41.
49. Schwenke DO, Pearson JT, Sonobe T, Ishibashi-Ueda H, Shimouchi A, Kangawa K, et al. Role of Rho-kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension. J Appl Physiol (1985) 2011; 110(4): 901-8.
50. Fukumoto Y., Yamada N., Matsubara H., Mizoguchi M., Uchino K., Yao A., et al. Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension. Circ J 2013, 77(10):2619-2625.
51. Asahara T., Murohara T., Sullivan A., Silver M., van der Zee R., Li T., et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997, 275(5302):964-967.
52. Koutroumpi M., Dimopoulos S., Psarra K., Kyprianou T., Nanas S. Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects. World J Cardiol 2012, 4(12):312-326.
53. Ward M.R., Stewart D.J., Kutryk M.J. Endothelial progenitor cell therapy for the treatment of coronary disease, acute MI, and pulmonary arterial hypertension: current perspectives. Catheter Cardiovasc Interv 2007, 70(7):983-998.
54. Asosingh K., Farha S., Lichtin A., Graham B., George D., Aldred M., et al. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension. Blood 2012, 120(6):1218-1227.
55. Bauer E.M., Shapiro R., Billiar T.R., Bauer P.M. High mobility group Box 1 inhibits human pulmonary artery endothelial cell migration via a Toll-like receptor 4- and interferon response factor 3-dependent mechanism(s). J Biol Chem 2013, 288(2):1365-1373.
56. Xia L., Zhu J.H., Qiu F.Y., Yang Y., Xie X.D., Wang X.X., et al. Senescent endothelial progenitor cells from dogs with pulmonary arterial hypertension: a before-after self-controlled study. J Physiol Sci 2009, 59(6):429-437.
57. Hansmann G., Plouffe B.D., Hatch A., von Gise A., Sallmon H., Zamanian R.T., et al. Design and validation of an endothelial progenitor cell capture chip and its application in patients with pulmonary arterial hypertension. J Mol Med (Berl) 2011, 89(10):971-983.
58. Levy M., Bonnet D., Mauge L., Celermajer D.S., Gaussem P., Smadja D.M. Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. PLoS One 2013, 8(6):e65114.
59. Diller G.P., van Eijl S., Okonko D.O., Howard L.S., Ali O., Thum T., et al. Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation 2008, 117(23):3020-3030.
60. Tanaka K., Sata M. Role of vascular progenitor cells in cardiovascular disease. Curr Pharm Des 2009, 15(24):2760-2768.
61. Schiavon M., Fadini G.P., Lunardi F., Agostini C., Boscaro E., Calabrese F., et al. Increased tissue endothelial progenitor cells in end-stage lung diseases with pulmonary hypertension. J Heart Lung Transplant 2012, 31(9):1025-1030.
62. Toshner M., Voswinckel R., Southwood M., Al-Lamki R., Howard L.S., Marchesan D., et al. Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension. Am J Respir Crit Care Med 2009, 180(8):780-787.
63. Yoder M.C., Mead L.E., Prater D., Krier T.R., Mroueh K.N., Li F., et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007, 109(5):1801-1809.
64. Ingram D.A., Mead L.E., Moore D.B., Woodard W., Fenoglio A., Yoder M.C. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood 2005, 105(7):2783-2786.
65. Baker C.D., Seedorf G.J., Wisniewski B.L., Black C.P., Ryan S.L., Balasubramaniam V., et al. Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 2013, 305(1):L73-L81.
66. Cheng C.C., Chang S.J., Chueh Y.N., Huang T.S., Huang P.H., Cheng S.M., et al. Distinct angiogenesis roles and surface markers of early and late endothelial progenitor cells revealed by functional group analyses. BMC Genomics 2013, 14:182.
67. Geti I., Ormiston M.L., Rouhani F., Toshner M., Movassagh M., Nichols J., et al. A practical and efficient cellular substrate for the generation of induced pluripotent stem cells from adults: blood-derived endothelial progenitor cells. Stem Cells Transl Med 2012, 1(12):855-865.
68. Tan K., Lessieur E., Cutler A., Nerone P., Vasanji A., Asosingh K., et al. Impaired function of circulating CD34(+) CD45(-) cells in patients with proliferative diabetic retinopathy. Exp Eye Res 2010, 91(2):229-237.
69. Stravodimou A., Voutsadakis I.A. Statin use and peripheral blood progenitor cells mobilization in patients with multiple myeloma. Clin Transl Oncol 2013.
70. Allegra A., Coppolino G., Bolignano D., Giacobbe M.S., Alonci A., D'Angelo A., et al. Endothelial progenitor cells: pathogenetic role and therapeutic perspectives. J Nephrol 2009, 22(4):463-475.
71. Rhodes C.J., Davidson A., Gibbs J.S., Wharton J., Wilkins M.R. Therapeutic targets in pulmonary arterial hypertension. Pharmacol Ther 2009, 121(1):69-88.
72. Stewart D.J., Mei S.H. Cell-based therapies for lung vascular diseases: lessons for the future. Proc Am Thorac Soc 2011, 8(6):535-540.
73. Anversa P., Perrella M.A., Kourembanas S., Choi A.M., Loscalzo J. Regenerative pulmonary medicine: potential and promise, pitfalls and challenges. Eur J Clin Invest 2012, 42(8):900-913.
74. Jones C.P., Rankin S.M. Bone marrow-derived stem cells and respiratory disease. Chest 2011, 140(1):205-211.
75. Baker C.D., Seedorf G.J., Wisniewski B.L., Black C.P., Ryan S.L., Balasubramaniam V., et al. Endothelial Colony-Forming Cell Conditioned Media Promotes Angiogenesis In Vitro and Prevents Pulmonary Hypertension in Experimental Bronchopulmonary Dysplasia. Am J Physiol Lung Cell Mol Physiol 2013.
76. Ormiston M.L., Deng Y., Stewart D.J., Courtman D.W. Innate immunity in the therapeutic actions of endothelial progenitor cells in pulmonary hypertension. Am J Respir Cell Mol Biol 2010, 43(5):546-554.
77. Conese M., Carbone A., Castellani S., Di Gioia S. Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases. Cells Tissues Organs 2013.
78. Xia L., Fu G.S., Yang J.X., Zhang F.R., Wang X.X. Endothelial progenitor cells may inhibit apoptosis of pulmonary microvascular endothelial cells: new insights into cell therapy for pulmonary arterial hypertension. Cytotherapy 2009, 11(4):492-502.
79. Zhu J.H., Wang X.X., Zhang F.R., Shang Y.P., Tao Q.M., Chen J.Z. Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study. Pediatr Transplant 2008, 12(6):650-655.
80. 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 Cardiol 2007, 49(14):1566-1571.
81. Yip H.K., Chang L.T., Sun C.K., Sheu J.J., Chiang C.H., Youssef A.A., et al. Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats. Crit Care Med 2008, 36(3):873-880.
82. Takahashi M., Nakamura T., Toba T., Kajiwara N., Kato H., Shimizu Y. Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng 2004, 10(5-6):771-779.
83. Marsboom G., Pokreisz P., Gheysens O., Vermeersch P., Gillijns H., Pellens M., et al. Sustained endothelial progenitor cell dysfunction after chronic hypoxia-induced pulmonary hypertension. Stem Cells 2008, 26(4):1017-1026.
84. Yen C.H., Tsai T.H., Leu S., Chen Y.L., Chang L.T., Chai H.T., et al. Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension. Cytotherapy 2013, 15(2):209-223.
85. Sun C.K., Lin Y.C., Yuen C.M., Chua S., Chang L.T., Sheu J.J., et al. Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats. Int J Cardiol 2012, 162(1):45-58.
86. Sun C.K., Lee F.Y., Sheu J.J., Yuen C.M., Chua S., Chung S.Y., et al. Early combined treatment with cilostazol and bone marrow-derived endothelial progenitor cells markedly attenuates pulmonary arterial hypertension in rats. J Pharmacol Exp Ther 2009, 330(3):718-726.
87. Smadja D.M., Mauge L., Gaussem P., d'Audigier C., Israel-Biet D., Celermajer D.S., et al. Treprostinil increases the number and angiogenic potential of endothelial progenitor cells in children with pulmonary hypertension. Angiogenesis 2011, 14(1):17-27.
88. Lavoie J.R., Stewart D.J. Genetically modified endothelial progenitor cells in the therapy of cardiovascular disease and pulmonary hypertension. Curr Vasc Pharmacol 2012, 10(3):289-299.
89. Coggins M.P., Bloch K.D. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol 2007, 27(9):1877-1885.
90. Wei L., Zhu W., Xia L., Yang Y., Liu H., Shen J., et al. Therapeutic effect of eNOS-transfected endothelial progenitor cells on hemodynamic pulmonary arterial hypertension. Hypertens Res 2013.
91. Campbell A.I., Kuliszewski M.A., Stewart D.J. Cell-based gene transfer to the pulmonary vasculature: Endothelial nitric oxide synthase overexpression inhibits monocrotaline-induced pulmonary hypertension. Am J Respir Cell Mol Biol 1999, 21(5):567-575.
92. 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 2001, 104(18):2242-2248.
93. Zhao Y.D., Courtman D.W., Deng Y., Kugathasan L., Zhang Q., Stewart D.J. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 2005, 96(4):442-450.
94. 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 2003, 108(7):889-895.
95. Nagaya N., Kangawa K. Adrenomedullin in the treatment of pulmonary hypertension. Peptides 2004, 25(11):2013-2018.
96. Nagaya N., Kangawa K. Adrenomedullin in pulmonary hypertension. Nihon Rinsho 2004, 62(Suppl 9):264-268.
97. Murakami S., Kimura H., Kangawa K., Nagaya N. Physiological significance and therapeutic potential of adrenomedullin in pulmonary hypertension. Cardiovasc Hematol Disord Drug Targets 2006, 6(2):125-132.
98. Zhao Q., Liu Z., Wang Z., Yang C., Liu J., Lu J. Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension. Ann Thorac Surg 2007, 84(2):544-552.