Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period

Circulation Research

Volumn 114, Issue 5, 2014, Pages 806-822

  Yao, Li Chin ^a   Testini, Chiara ^b   Tvorogov, Denis ^c   Anisimov, Andrey ^c   Vargas, Sara O ^d   Baluk, Peter ^a   Pytowski, Bronislaw ^e   Claesson Welsh, Lena ^b   Alitalo, Kari ^c   McDonald, Donald M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UPPSALA UNIVERSITY   (Sweden)

^c UNIVERSITY OF HELSINKI   (Finland)

^d HARVARD MEDICAL SCHOOL   (United States)

^e ELI LILLY AND COMPANY   (United States)

Author keywords

Chylothorax; lung; lymphangiogenesis; lymphangiomatosis; lymphatic vessels; pulmonary; pulmonary edema; VEGFR 2; VEGFR 3

Indexed keywords

DOXYCYCLINE; HETERODIMER; SECRETORY PROTEIN; TETRACYCLINE; TRANSACTIVATOR PROTEIN; VASCULOTROPIN C; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHYLOTHORAX; CLARA CELL; CONTROLLED STUDY; CRITICAL ILLNESS; GENE OVEREXPRESSION; HUMAN; HUMAN TISSUE; LUNG BLOOD VESSEL; LYMPH VESSEL; LYMPHANGIECTASIS; LYMPHANGIOGENESIS; MOUSE; NONHUMAN; PLEURA; POSTNATAL CARE; PRIORITY JOURNAL; PULMONARY LYMPHANGIECTASIA; RESPIRATORY DISTRESS; RESPIRATORY EPITHELIUM; TRANSGENIC MOUSE;

CHYLOTHORAX; LUNG; LYMPHANGIOGENESIS; LYMPHANGIOMATOSIS, PULMONARY; LYMPHATIC VESSELS; PULMONARY EDEMA; VEGFR-2; VEGFR-3;

ANIMALS; FEMALE; HUMANS; INFANT; LUNG DISEASES; LYMPHANGIECTASIS; LYMPHATIC VESSELS; MALE; MICE; MICE, INBRED STRAINS; MICE, TRANSGENIC; PREGNANCY; PULMONARY EDEMA; SIGNAL TRANSDUCTION; TRACHEA; UTEROGLOBIN; VASCULAR ENDOTHELIAL GROWTH FACTOR C; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3;

EID: 84895923922     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.303119     Document Type: Article

References (72)

1. Leak LV. Lymphatic removal of fluids and particles in the mammalian lung. Environ Health Perspect. 1980;35:55-75.
2. Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol. 2005;5:617-628.
3. El-Chemaly S, Levine SJ, Moss J. Lymphatics in lung disease. Ann N Y Acad Sci. 2008;1131:195-202.
4. Bredt H. Lymphangiectasia pulmonum congenita. Virchows Arch. 1952;321:517-530.
5. Laurence KM. Congenital pulmonary cystic lymphangiectasis. J Pathol Bacteriol. 1955;70:325-333.
6. Noonan JA, Walters LR, Reeves JT. Congenital pulmonary lymphangiectasis. Am J Dis Child. 1970;120:314-319.
7. Virchow R. Zur Entwicklungsgeschichte des Cretinismus und Der Schdeldifformitten. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin. Frankfurt-am-Main: Verlag von Meidinger Sohn & Company. 1856;983-984.
8. Faul JL, Berry GJ, Colby TV, Ruoss SJ, Walter MB, Rosen GD, Raffin TA. Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome. Am J Respir Crit Care Med. 2000;161:1037-1046.
9. Barker PM, Esther CR Jr, Fordham LA, Maygarden SJ, Funkhouser WK. Primary pulmonary lymphangiectasia in infancy and childhood. Eur Respir J. 2004;24:413-419.
10. Esther CR Jr, Barker PM. Pulmonary lymphangiectasia: Diagnosis and clinical course. Pediatr Pulmonol. 2004;38:308-313.
11. Bellini C, Boccardo F, Campisi C, Bonioli E. Congenital pulmonary lymphangiectasia. Orphanet J Rare Dis. 2006;1:43.
12. Finder J, Steinfeld J. Congenital pulmonary lymphangiectasia. N Engl J Med. 2004;350:948; author reply 948.
13. Boon LM, Vikkula M. Molecular genetics of vascular malformations. In: Mulliken JB, Burrows PE, Fishman SJ, eds. Mulliken & Youngs Vascular Anomalies: Hemangiomas and Malformations. Oxford: Oxford University Press; 2013:327-375.
14. Tazelaar HD, Kerr D, Yousem SA, Saldana MJ, Langston C, Colby TV. Diffuse pulmonary lymphangiomatosis. Hum Pathol. 1993;24:1313-1322.
15. Hassanein AH, Mulliken JB, Fishman SJ, Quatrano NA, Zurakowski D, Greene AK. Lymphatic malformation: Risk of progression during childhood and adolescence. J Craniofac Surg. 2012;23:149-152.
16. Fishman SJ. Truncal, Visceral, and Genital Vascular Malformations. In: Mulliken JB, Burrows PE, Fishman SJ, eds. Mulliken & Youngs Vascular Anomalies: Hemangiomas and Malformations. Oxford: Oxford University Press; 2013:966-1016.
17. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5:74-80.
18. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276:1423-1425.
19. Lohela M, Heloter H, Haiko P, Dumont DJ, Alitalo K. Transgenic induction of vascular endothelial growth factor-C is strongly angiogenic in mouse embryos but leads to persistent lymphatic hyperplasia in adult tissues. Am J Pathol. 2008;173:1891-1901.
20. Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA, Yl-Herttuala S, Jackson DG, Alitalo K, McDonald DM. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest. 2005;115:247-257.
21. Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, Saksela O, Kalkkinen N, Alitalo K. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 1997;16:3898-3911.
22. Hong YK, Lange-Asschenfeldt B, Velasco P, Hirakawa S, Kunstfeld R, Brown LF, Bohlen P, Senger DR, Detmar M. VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha-1beta1 and alpha2beta1 integrins. FASEB J. 2004;18:1111-1113.
23. Goldman J, Rutkowski JM, Shields JD, Pasquier MC, Cui Y, Schmkel HG, Willey S, Hicklin DJ, Pytowski B, Swartz MA. Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis. FASEB J. 2007;21:1003-1012.
24. Baldwin ME, Halford MM, Roufail S, Williams RA, Hibbs ML, Grail D, Kubo H, Stacker SA, Achen MG. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol Cell Biol. 2005;25:2441-2449.
25. Haiko P, Makinen T, Keskitalo S, Taipale J, Karkkainen MJ, Baldwin ME, Stacker SA, Achen MG, Alitalo K. Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol Cell Biol. 2008;28:4843-4850.
26. Baluk P, Hogmalm A, Bry M, Alitalo K, Bry K, McDonald DM. Transgenic overexpression of interleukin-1beta induces persistent lymphangiogenesis but not angiogenesis in mouse airways. Am J Pathol. 2013
27. Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, Vestweber D, Corada M, Molendini C, Dejana E, McDonald DM. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med. 2007;204:2349-2362.
28. Yao LC, Baluk P, Srinivasan RS, Oliver G, McDonald DM. Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Am J Pathol. 2012;180:2561-2575.
29. Huggenberger R, Siddiqui SS, Brander D, Ullmann S, Zimmermann K, Antsiferova M, Werner S, Alitalo K, Detmar M. An important role of lymphatic vessel activation in limiting acute inflammation. Blood. 2011;117:4667-4678.
30. Zhou Q, Guo R, Wood R, Boyce BF, Liang Q, Wang YJ, Schwarz EM, Xing L. Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice. Arthritis Rheum. 2011;63:2318-2328.
31. Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, Kang MJ, Cohn L, Kim YK, McDonald DM, Elias JA. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med. 2004;10:1095-1103.
32. Baluk P, Lee CG, Link H, Ator E, Haskell A, Elias JA, McDonald DM. Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways. Am J Pathol. 2004;165:1071-1085.
33. Tichelaar JW, Lu W, Whitsett JA. Conditional expression of fibroblast growth factor-7 in the developing and mature lung. J Biol Chem. 2000;275:11858-11864.
34. Perl AK, Tichelaar JW, Whitsett JA. Conditional gene expression in the respiratory epithelium of the mouse. Transgenic Res. 2002;11:21-29.
35. Choi I, Chung HK, Ramu S, Lee HN, Kim KE, Lee S, Yoo J, Choi D, Lee YS, Aguilar B, Hong YK. Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse. Blood. 2011;117:362-365.
36. Bry K, Whitsett JA, Lappalainen U. IL-1beta disrupts postnatal lung morphogenesis in the mouse. Am J Respir Cell Mol Biol. 2007;36:32-42.
37. Nilsson I, Bahram F, Li X, Gualandi L, Koch S, Jarvius M, Sderberg O, Anisimov A, Kholov I, Pytowski B, Baldwin M, Yl-Herttuala S, Alitalo K, Kreuger J, Claesson-Welsh L. VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010;29:1377-1388.
38. Kerjaschki D, Sharkey DJ, Farquhar MG. Identification and characterization of podocalyxin-the major sialoprotein of the renal glomerular epithelial cell. J Cell Biol. 1984;98:1591-1596.
39. McLaughlin RF Jr, Tyler WS, Canada RO. Subgross pulmonary anatomy of the rabbit, rat, and guinea pig, with additional notes on the human lung. Am Rev Respir Dis. 1966;94:380-387.
40. Kretschmer S, Dethlefsen I, Hagner-Benes S, Marsh LM, Garn H, Knig P. Visualization of intrapulmonary lymph vessels in healthy and inflamed murine lung using CD90/Thy-1 as a marker. PLoS One. 2013;8:e55201.
41. Pack RJ, Al-Ugaily LH, Morris G. The cells of the tracheobronchial epithelium of the mouse: A quantitative light and electron microscope study. J Anat. 1981;132:71-84.
42. Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lbbert H, Bujard H. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA. 1996;93:10933-10938.
43. Krebs R, Tikkanen JM, Ropponen JO, Jeltsch M, Jokinen JJ, Yl-Herttuala S, Nyknen AI, Lemstrm KB. Critical role of VEGF-C/VEGFR-3 signaling in innate and adaptive immune responses in experimental obliterative bronchiolitis. Am J Pathol. 2012;181:1607-1620.
44. Bletsa A, Virtej A, Berggreen E. Vascular endothelial growth factors and receptors are up-regulated during development of apical periodontitis. J Endod. 2012;38:628-635.
45. Ni A, Lashnits E, Yao LC, Baluk P, McDonald DM. Rapid remodeling of airway vascular architecture at birth. Dev Dyn. 2010;239:2354-2366.
46. Milch RA, Rall DP, Tobie JE. Bone localization of the tetracyclines. J Natl Cancer Inst. 1957;19:87-93.
47. Deng Y, Atri D, Eichmann A, Simons M. Endothelial ERK signaling controls lymphatic fate specification. J Clin Invest. 2013;123:1202-1215.
48. Mouta-Bellum C, Kirov A, Miceli-Libby L, Mancini ML, Petrova TV, Liaw L, Prudovsky I, Thorpe PE, Miura N, Cantley LC, Alitalo K, Fruman DA, Vary CP. Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85alpha, p55alpha, and p50alpha. Dev Dyn. 2009;238:2670-2679.
49. Mettauer N, Agrawal S, Pierce C, Ashworth M, Petros A. Outcome of children with pulmonary lymphangiectasis. Pediatr Pulmonol. 2009;44:351-357.
50. Felman AH, Rhatigan RM, Pierson KK. Pulmonary lymphangiectasia. Observation in 17 patients and proposed classification. Am J Roentgenol Radium Ther Nucl Med. 1972;116:548-558.
51. Bouchard S, Di Lorenzo M, Youssef S, Simard P, Lapierre JG. Pulmonary lymphangiectasia revisited. J Pediatr Surg. 2000;35:796-800.
52. Scalzetti EM, Heitzman ER, Groskin SA, Randall PA, Katzenstein AL. Developmental lymphatic disorders of the thorax. Radiographics. 1991;11:1069-1085.
53. Gould SJ, Webb AK, Kelsey A. Congenital abnormalities and pediatric lung disease, including neoplasms. In: Haselton P, Flieder DB, eds. Spencers Pathology of the Lung. New York, NY: Cambridge University Press; 2013:66-145.
54. Allen TC, Cagle PT, Flieder DB. Mesenchymal and miscellaneous neoplasms. In: Haselton P, Flieder DB, eds. Spencers Pathology of the Lung. New York, NY: Cambridge University Press; 2013:1224-1315.
55. El-Chemaly S, Malide D, Zudaire E, et al. Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms. Proc Natl Acad Sci USA. 2009;106:3958-3963.
56. Das S, Ladell DS, Podgrabinska S, Ponomarev V, Nagi C, Fallon JT, Skobe M. Vascular endothelial growth factor-C induces lymphangitic carcinomatosis, an extremely aggressive form of lung metastases. Cancer Res. 2010;70:1814-1824.
57. Perl AK, Zhang L, Whitsett JA. Conditional expression of genes in the respiratory epithelium in transgenic mice: Cautionary notes and toward building a better mouse trap. Am J Respir Cell Mol Biol. 2009;40:1-3.
58. Duerr J, Gruner M, Schubert SC, Haberkorn U, Bujard H, Mall MA. Use of a new-generation reverse tetracycline transactivator system for quantitative control of conditional gene expression in the murine lung. Am J Respir Cell Mol Biol. 2011;44:244-254.
59. Anisimov A, Alitalo A, Korpisalo P, Soronen J, Kaijalainen S, Leppnen VM, Jeltsch M, Yl-Herttuala S, Alitalo K. Activated forms of VEGF-C and VEGF-D provide improved vascular function in skeletal muscle. Circ Res. 2009;104:1302-1312.
60. Stacker SA, Stenvers K, Caesar C, Vitali A, Domagala T, Nice E, Roufail S, Simpson RJ, Moritz R, Karpanen T, Alitalo K, Achen MG. Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers. J Biol Chem. 1999;274:32127-32136.
61. Harris NC, Davydova N, Roufail S, Paquet-Fifield S, Paavonen K, Karnezis T, Zhang YF, Sato T, Rothacker J, Nice EC, Stacker SA, Achen MG. The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology. J Biol Chem. 2013;288:8176-8186.
62. Ferrara N. Binding to the extracellular matrix and proteolytic processing: Two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell. 2010;21:687-690.
63. Tammela T, He Y, Lyytikk J, Jeltsch M, Markkanen J, Pajusola K, Yl-Herttuala S, Alitalo K. Distinct architecture of lymphatic vessels induced by chimeric vascular endothelial growth factor-C/vascular endothelial growth factor heparin-binding domain fusion proteins. Circ Res. 2007;100:1468-1475.
64. Yin X, Johns SC, Lawrence R, Xu D, Reddi K, Bishop JR, Varner JA, Fuster MM. Lymphatic endothelial heparan sulfate deficiency results in altered growth responses to vascular endothelial growth factor-C (VEGF-C). J Biol Chem. 2011;286:14952-14962.
65. Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, Kubo H, Thurston G, McDonald DM, Achen MG, Stacker SA, Alitalo K. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001;20:1223-1231.
66. Dixelius J, Makinen T, Wirzenius M, Karkkainen MJ, Wernstedt C, Alitalo K, Claesson-Welsh L. Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites. J Biol Chem. 2003;278:40973-40979.
67. Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011;17: 1371-1380.
68. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling-in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359-371.
69. Tvorogov D, Anisimov A, Zheng W, Leppnen VM, Tammela T, Laurinavicius S, Holnthoner W, Heloter H, Holopainen T, Jeltsch M, Kalkkinen N, Lankinen H, Ojala PM, Alitalo K. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell. 2010;18: 630-640.
70. Yao LC, Baluk P, Feng J, McDonald DM. Steroid-resistant lymphatic remodeling in chronically inflamed mouse airways. Am J Pathol. 2010;176:1525-1541.
71. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10:417-427.
72. Liao S, Liu J, Lin P, Shi T, Jain RK, Xu L. TGF-beta blockade controls ascites by preventing abnormalization of lymphatic vessels in orthotopic human ovarian carcinoma models. Clin Cancer Res. 2011;17:1415-1424.