Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-cf6xr Total loading time: 0 Render date: 2025-05-06T02:16:33.714Z Has data issue: false hasContentIssue false

Chapter 3 - Pulmonary Vascular Development

Published online by Cambridge University Press:  05 April 2016

By
Timothy D. Le Cras  and
Marlene Rabinovitch
Edited by
Alan H. Jobe ,
Jeffrey A. Whitsett  and
Steven H. Abman
Alan H. Jobe
Affiliation:
University of Cincinnati
Jeffrey A. Whitsett
Affiliation:
Cincinnati Children’s Hospital
Steven H. Abman
Affiliation:
University of Colorado School of Medicine
Get access

Summary

Abstract

The lung is the most vascularized organ in the body due to its primary function to perform exchange of respiratory gases for the entire body. This chapter reviews the structure, developmental origins, timing, and patterning of the arterial, capillary, venous, and lymphatic systems in the lung as well as the main pulmonary arteries and veins that connect the heart to the lung. Both the pre- and postnatal stages (phases) of pulmonary vascular morphogenesis are covered. The relative importance of vasculogenesis versus angiogenesis in the initial formation of pulmonary vessels is discussed as well as other potential mechanisms. Current knowledge of cellular and molecular pathways and mechanisms that orchestrate and regulate vascular morphogenesis are discussed, along with the relative contributions of endothelial cells, smooth muscle cells, pericytes, and fibroblasts. The coordinate regulation of the pulmonary vascular system with airway development is critical and is also reviewed. Responses of the pulmonary circulation to injury and the potential for regression and regeneration of the lung vasculature as well as unanswered questions and future directions in pulmonary vascular development are also presented.

Type
Chapter
Information
Fetal and Neonatal Lung Development
Clinical Correlates and Technologies for the Future
 , pp. 34 - 57
Publisher: Cambridge University Press
Print publication year: 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Schachtner, SK, Wang, Y, Scott Baldwin, H. Qualitative and quantitative analysis of embryonic pulmonary vessel formation. American Journal of Respiratory Cell and Molecular Biology. 2000;22(2):157–165.CrossRefGoogle ScholarPubMed
Glenny, RW. Emergence of matched airway and vascular trees from fractal rules. Journal of Applied Physiology. 2011;110(4):1119–1129.CrossRefGoogle ScholarPubMed
Hislop, A. Developmental biology of the pulmonary circulation. Paediatric Respiratory Reviews. 2005;6(1):35–43.CrossRefGoogle ScholarPubMed
deMello, DE, Sawyer, D, Galvin, N, Reid, LM. Early fetal development of lung vasculature. American Journal of Respiratory Cell and Molecular Biology. 1997;16(5):568–581.CrossRefGoogle ScholarPubMed
Peng, T, Tian, Y, Boogerd, CJ, Lu, MM, Kadzik, RS, Stewart, KM, et al. Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor. Nature. 2013;500(7464):589–592.CrossRefGoogle ScholarPubMed
Galambos, C, deMello, DE. Molecular mechanisms of pulmonary vascular development. Pediatric and Developmental Pathology. 2007;10(1):1–17.CrossRefGoogle ScholarPubMed
Djonov, V, Schmid, M, Tschanz, SA, Burri, PH. Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circulation Research. 2000;86(3):286–292.CrossRefGoogle ScholarPubMed
Greif, DM, Kumar, M, Lighthouse, JK, Hum, J, An, A, Ding, L, et al. Radial construction of an arterial wall. Developmental Cell. 2012;23(3):482–493.CrossRefGoogle ScholarPubMed
Hall, SM, Hislop, AA, Haworth, SG. Origin, differentiation, and maturation of human pulmonary veins. American Journal of Respiratory Cell and Molecular Biology. 2002;26(3):333–340.CrossRefGoogle ScholarPubMed
Thebaud, B, Abman, SH. Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. American Journal of Respiratory and Critical Care Medicine. 2007;175(10):978–985.CrossRefGoogle ScholarPubMed
Bellusci, S, Furuta, Y, Rush, MG, Henderson, R, Winnier, G, Hogan, BL. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development. 1997;124(1):53–63.CrossRefGoogle ScholarPubMed
Miller, LA, Wert, SE, Clark, JC, Xu, Y, Perl, AK, Whitsett, JA. Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung. Developmental Dynamics. 2004;231(1):57–71.CrossRefGoogle ScholarPubMed
Amaya, E, Musci, TJ, Kirschner, MW. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell. 1991;66(2):257–270.CrossRefGoogle ScholarPubMed
Flamme, I, Breier, G, Risau, W. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. Developmental Biology. 1995;169(2):699–712.CrossRefGoogle ScholarPubMed
Cox, CM, Poole, TJ. Angioblast differentiation is influenced by the local environment: FGF-2 induces angioblasts and patterns vessel formation in the quail embryo. Developmental Dynamics. 2000;218(2):371–382.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Gonzalez, AM, Hill, DJ, Logan, A, Maher, PA, Baird, A. Distribution of fibroblast growth factor (FGF)-2 and FGF receptor-1 messenger RNA expression and protein presence in the mid-trimester human fetus. Pediatric Research. 1996;39(3):375–385.CrossRefGoogle ScholarPubMed
Shannon, JM, Hyatt, BA. Epithelial-mesenchymal interactions in the developing lung. Annual Review of Physiology. 2004;66:625–645.CrossRefGoogle ScholarPubMed
Serls, AE, Doherty, S, Parvatiyar, P, Wells, JM, Deutsch, GH. Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development. 2005;132(1):35–47.CrossRefGoogle ScholarPubMed
Zachary, I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. American Journal of Physiology Cell Physiology. 2001;280(6):C1375–1386.CrossRefGoogle ScholarPubMed
Ferrara, N, Gerber, HP, LeCouter, J. The biology of VEGF and its receptors. Nature Medicine. 2003;9(6):669–676.CrossRefGoogle ScholarPubMed
Shalaby, F, Rossant, J, Yamaguchi, TP, Gertsenstein, M, Wu, XF, Breitman, ML, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376(6535):62–66.CrossRefGoogle ScholarPubMed
Tischer, E, Mitchell, R, Hartman, T, Silva, M, Gospodarowicz, D, Fiddes, JC, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. The Journal of Biological Chemistry. 1991;266(18):11947–11954.CrossRefGoogle ScholarPubMed
Ng, YS, Rohan, R, Sunday, ME, deMello, DE, D'Amore, PA. Differential expression of VEGF isoforms in mouse during development and in the adult. Developmental Dynamics. 2001;220(2):112–121.3.0.CO;2-D>CrossRefGoogle ScholarPubMed
Gebb, SA, Shannon, JM. Tissue interactions mediate early events in pulmonary vasculogenesis. Developmental Dynamics. 2000;217(2):159–69.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Galambos, C, Ng, YS, Ali, A, Noguchi, A, Lovejoy, S, D'Amore, PA, et al. Defective pulmonary development in the absence of heparin-binding vascular endothelial growth factor isoforms. American Journal of Respiratory Cell and Molecular Biology. 2002;27(2):194–203.CrossRefGoogle ScholarPubMed
Gerber, HP, Hillan, KJ, Ryan, AM, Kowalski, J, Keller, GA, Rangell, L, et al. VEGF is required for growth and survival in neonatal mice. Development. 1999;126(6):1149–1159.CrossRefGoogle ScholarPubMed
Le Cras, TD, Markham, NE, Tuder, RM, Voelkel, NF, Abman, SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. American Journal of Physiology Lung Cellular and Molecular Physiology. 2002;283(3):L555–562.CrossRefGoogle ScholarPubMed
Zeng, X, Wert, SE, Federici, R, Peters, KG, Whitsett, JA. VEGF enhances pulmonary vasculogenesis and disrupts lung morphogenesis in vivo. Developmental Dynamics. 1998;211(3):215–227.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Akeson, AL, Greenberg, JM, Cameron, JE, Thompson, FY, Brooks, SK, Wiginton, D, et al. Temporal and spatial regulation of VEGF-A controls vascular patterning in the embryonic lung. Developmental Biology. 2003;264(2):443–455.CrossRefGoogle ScholarPubMed
Le Cras, TD, Spitzmiller, RE, Albertine, KH, Greenberg, JM, Whitsett, JA, Akeson, AL. VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. American Journal of Physiology Lung Cellular and Molecular Physiology. 2004;287(1):L134–142.CrossRefGoogle ScholarPubMed
Greenberg, JM, Thompson, FY, Brooks, SK, Shannon, JM, McCormick-Shannon, K, Cameron, JE, et al. Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung. Developmental Dynamics. 2002;224(2):144–153.CrossRefGoogle Scholar
Schreiber, AB, Winkler, ME, Derynck, R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986;232(4755):1250–1253.CrossRefGoogle ScholarPubMed
Pardanaud, L, Dieterlen-Lievre, F. Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo. Development. 1999;126(4):617–627.CrossRefGoogle ScholarPubMed
Korfhagen, TR, Swantz, RJ, Wert, SE, McCarty, JM, Kerlakian, CB, Glasser, SW, et al. Respiratory epithelial cell expression of human transforming growth factor-alpha induces lung fibrosis in transgenic mice. The Journal of Clinical Investigation. 1994;93(4):1691–1699.CrossRefGoogle ScholarPubMed
Hardie, WD, Bruno, MD, Huelsman, KM, Iwamoto, HS, Carrigan, PE, Leikauf, GD, et al. Postnatal lung function and morphology in transgenic mice expressing transforming growth factor-alpha. The American Journal of Pathology. 1997;151(4):1075–1083.Google ScholarPubMed
Le Cras, TD, Hardie, WD, Fagan, K, Whitsett, JA, Korfhagen, TR. Disrupted pulmonary vascular development and pulmonary hypertension in transgenic mice overexpressing transforming growth factor-alpha. American Journal of Physiology Lung Cellular and Molecular Physiology. 2003;285(5):L1046–1054.CrossRefGoogle ScholarPubMed
Madtes, DK, Elston, AL, Hackman, RC, Dunn, AR, Clark, JG. Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice. American Journal of Respiratory Cell and Molecular Biology. 1999;20(5):924–934.CrossRefGoogle ScholarPubMed
Thurston, G, Gale, NW. Vascular endothelial growth factor and other signaling pathways in developmental and pathologic angiogenesis. International Journal of Hematology. 2004;80(1):7–20.CrossRefGoogle ScholarPubMed
Du, L, Sullivan, CC, Chu, D, Cho, AJ, Kido, M, Wolf, PL, et al. Signaling molecules in nonfamilial pulmonary hypertension. The New England Journal of Medicine. 2003;348(6):500–509.CrossRefGoogle ScholarPubMed
Sullivan, CC, Du, L, Chu, D, Cho, AJ, Kido, M, Wolf, PL, et al. Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(21):12331–12336.CrossRefGoogle ScholarPubMed
Chinoy, MR. Pulmonary hypoplasia and congenital diaphragmatic hernia: advances in the pathogenetics and regulation of lung development. The Journal of Surgical Research. 2002;106(1):209–223.CrossRefGoogle ScholarPubMed
Weinmaster, G. The ins and outs of notch signaling. Molecular and Cellular Neurosciences. 1997;9(2):91–102.CrossRefGoogle ScholarPubMed
Krebs, LT, Xue, Y, Norton, CR, Shutter, JR, Maguire, M, Sundberg, JP, et al. Notch signaling is essential for vascular morphogenesis in mice. Genes & Development. 2000;14(11):1343–1352.CrossRefGoogle ScholarPubMed
Xue, Y, Gao, X, Lindsell, CE, Norton, CR, Chang, B, Hicks, C, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Human Molecular Genetics. 1999;8(5):723–730.CrossRefGoogle ScholarPubMed
Lawson, ND, Scheer, N, Pham, VN, Kim, CH, Chitnis, AB, Campos-Ortega, JA, et al. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development. 2001;128(19):3675–3683.CrossRefGoogle ScholarPubMed
Zhong, TP, Childs, S, Leu, JP, Fishman, MC. Gridlock signalling pathway fashions the first embryonic artery. Nature. 2001;414(6860):216–220.CrossRefGoogle ScholarPubMed
Visconti, RP, Richardson, CD, Sato, TN. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proceedings of the National Academy of Sciences of the United States of America. 2002;99(12):8219–8224.CrossRefGoogle ScholarPubMed
Fischer, A, Schumacher, N, Maier, M, Sendtner, M, Gessler, M. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes & Development. 2004;18(8):901–911.CrossRefGoogle ScholarPubMed
Domenga, V, Fardoux, P, Lacombe, P, Monet, M, Maciazek, J, Krebs, LT, et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes & Development. 2004;18(22):2730–2735.CrossRefGoogle ScholarPubMed
Kong, Y, Glickman, J, Subramaniam, M, Shahsafaei, A, Allamneni, KP, Aster, JC, et al. Functional diversity of notch family genes in fetal lung development. American Journal of Physiology Lung Cellular and Molecular Physiology. 2004;286(5):L1075–1083.CrossRefGoogle ScholarPubMed
Kalinichenko, VV, Gusarova, GA, Kim, IM, Shin, B, Yoder, HM, Clark, J, et al. Foxf1 haploinsufficiency reduces Notch-2 signaling during mouse lung development. American Journal of Physiology Lung Cellular and Molecular Physiology. 2004;286(3):L521–530.CrossRefGoogle ScholarPubMed
Darland, DC, D'Amore, PA. TGF beta is required for the formation of capillary-like structures in three-dimensional cocultures of 10T1/2 and endothelial cells. Angiogenesis. 2001;4(1):11–20.CrossRefGoogle ScholarPubMed
Roberts, AB, Sporn, MB. Regulation of endothelial cell growth, architecture, and matrix synthesis by TGF-beta. The American Review of Respiratory Disease. 1989;140(4):1126–1128.CrossRefGoogle ScholarPubMed
Li, DY, Sorensen, LK, Brooke, BS, Urness, LD, Davis, EC, Taylor, DG, et al. Defective angiogenesis in mice lacking endoglin. Science. 1999;284(5419):1534–1537.CrossRefGoogle ScholarPubMed
Jonker, L, Arthur, HM. Endoglin expression in early development is associated with vasculogenesis and angiogenesis. Mechanisms of Development. 2002;110(1–2):193–196.CrossRefGoogle ScholarPubMed
Oh, SP, Seki, T, Goss, KA, Imamura, T, Yi, Y, Donahoe, PK, et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(6):2626–2631.CrossRefGoogle ScholarPubMed
Urness, LD, Sorensen, LK, Li, DY. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nature Genetics. 2000;26(3):328–331.CrossRefGoogle ScholarPubMed
Nakagawa, T, Li, JH, Garcia, G, Mu, W, Piek, E, Bottinger, EP, et al. TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways. Kidney International. 2004;66(2):605–613.CrossRefGoogle ScholarPubMed
Cai, J, Pardali, E, Sanchez-Duffhues, G, ten Dijke, P. BMP signaling in vascular diseases. FEBS Letters. 2012;586(14):1993–2002.CrossRefGoogle ScholarPubMed
Volpert, OV, Pili, R, Sikder, HA, Nelius, T, Zaichuk, T, Morris, C, et al. Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1. Cancer Cell. 2002;2(6):473–483.CrossRefGoogle ScholarPubMed
International, PPHC, Lane, KB, Machado, RD, Pauciulo, MW, Thomson, JR, Phillips, JA, 3rd, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nature Genetics. 2000;26(1):81–84.Google Scholar
Itoh, F, Itoh, S, Goumans, MJ, Valdimarsdottir, G, Iso, T, Dotto, GP, et al. Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells. The EMBO Journal. 2004;23(3):541–551.CrossRefGoogle ScholarPubMed
de Jesus Perez, VA, Alastalo, TP, Wu, JC, Axelrod, JD, Cooke, JP, Amieva, M, et al. Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-beta-catenin and Wnt-RhoA-Rac1 pathways. The Journal of Cell Biology. 2009;184(1):83–99.CrossRefGoogle ScholarPubMed
Alastalo, TP, Li, M, de Jesus Perez, V, Pham, D, Sawada, H, Wang, JK, et al. Disruption of PPARgamma/beta-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. The Journal of Clinical Investigation. 2011;121(9):3735–3746.CrossRefGoogle ScholarPubMed
de Jesus Perez, VA, Ali, Z, Alastalo, TP, Ikeno, F, Sawada, H, Lai, YJ, et al. BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. The Journal of Cell Biology. 2011;192(1):171–188.CrossRefGoogle Scholar
Zerlin, M, Julius, MA, Kitajewski, J. Wnt/Frizzled signaling in angiogenesis. Angiogenesis. 2008;11(1):63–69.CrossRefGoogle ScholarPubMed
Wright, M, Aikawa, M, Szeto, W, Papkoff, J. Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells. Biochemical and Biophysical Research Communications. 1999;263(2):384–388.CrossRefGoogle ScholarPubMed
Monkley, SJ, Delaney, SJ, Pennisi, DJ, Christiansen, JH, Wainwright, BJ. Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996;122(11):3343–3353.CrossRefGoogle ScholarPubMed
Shu, W, Jiang, YQ, Lu, MM, Morrisey, EE. Wnt7b regulates mesenchymal proliferation and vascular development in the lung. Development. 2002;129(20):4831–4842.CrossRefGoogle ScholarPubMed
Cohen, ED, Ihida-Stansbury, K, Lu, MM, Panettieri, RA, Jones, PL, Morrisey, EE. Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway. The Journal of Clinical Investigation. 2009;119(9):2538–2549.CrossRefGoogle Scholar
Andrae, J, Gallini, R, Betsholtz, C. Role of platelet-derived growth factors in physiology and medicine. Genes & Development. 2008;22(10):1276–1312.CrossRefGoogle ScholarPubMed
Betsholtz, C. Biology of platelet-derived growth factors in development. Birth Defects Research Part C, Embryo Today: Reviews. 2003;69(4):272–285.CrossRefGoogle ScholarPubMed
Yamashita, J, Itoh, H, Hirashima, M, Ogawa, M, Nishikawa, S, Yurugi, T, et al. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature. 2000;408(6808):92–96.CrossRefGoogle ScholarPubMed
Grimminger, F, Schermuly, RT. PDGF receptor and its antagonists: role in treatment of PAH. Advances in Experimental Medicine and Biology. 2010;661:435–446.CrossRefGoogle ScholarPubMed
Dupont, J, Holzenberger, M. Biology of insulin-like growth factors in development. Birth Defects Research Part C, Embryo Today: Reviews. 2003;69(4):257–271.CrossRefGoogle ScholarPubMed
Han, RN, Post, M, Tanswell, AK, Lye, SJ. Insulin-like growth factor-I receptor-mediated vasculogenesis/angiogenesis in human lung development. American Journal of Respiratory Cell and Molecular Biology. 2003;28(2):159–169.CrossRefGoogle ScholarPubMed
Salvucci, O, Tosato, G. Essential roles of EphB receptors and EphrinB ligands in endothelial cell function and angiogenesis. Advances in Cancer Research. 2012;114:21–57.CrossRefGoogle ScholarPubMed
Wang, HU, Chen, ZF, Anderson, DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93(5):741–753.CrossRefGoogle ScholarPubMed
Adams, RH, Wilkinson, GA, Weiss, C, Diella, F, Gale, NW, Deutsch, U, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes & Development. 1999;13(3):295–306.CrossRefGoogle ScholarPubMed
Shin, D, Garcia-Cardena, G, Hayashi, S, Gerety, S, Asahara, T, Stavrakis, G, et al. Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization. Developmental Biology. 2001;230(2):139–150.CrossRefGoogle ScholarPubMed
Baldwin, HS. Early embryonic vascular development. Cardiovascular Research. 1996;31 Spec No:E34–45.CrossRefGoogle Scholar
Tabruyn, SP, Griffioen, AW. Molecular pathways of angiogenesis inhibition. Biochemical and Biophysical Research Communications. 2007;355(1):1–5.CrossRefGoogle ScholarPubMed
Lawler, J, Sunday, M, Thibert, V, Duquette, M, George, EL, Rayburn, H, et al. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. The Journal of Clinical Investigation. 1998;101(5):982–992.CrossRefGoogle ScholarPubMed
Crawford, SE, Stellmach, V, Murphy-Ullrich, JE, Ribeiro, SM, Lawler, J, Hynes, RO, et al. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 1998;93(7):1159–1170.CrossRefGoogle Scholar
Tang, JR, Karumanchi, SA, Seedorf, G, Markham, N, Abman, SH. Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia. American Journal of Physiology Lung Cellular and Molecular Physiology. 2012;302(1):L36–46.CrossRefGoogle ScholarPubMed
Schwarz, M, Lee, M, Zhang, F, Zhao, J, Jin, Y, Smith, S, et al. EMAP II: a modulator of neovascularization in the developing lung. The American Journal of Physiology. 1999;276(2 Pt 1):L365–375.Google ScholarPubMed
Mujahid, S, Nielsen, HC, Volpe, MV. MiR-221 and miR-130a regulate lung airway and vascular development. PLoS One. 2013;8(2):e55911.CrossRefGoogle ScholarPubMed
De Val, S, Black, BL. Transcriptional control of endothelial cell development. Developmental Cell. 2009;16(2):180–195.CrossRefGoogle ScholarPubMed
Swift, MR, Weinstein, BM. Arterial-venous specification during development. Circulation Research. 2009;104(5):576–588.CrossRefGoogle ScholarPubMed
Park, C, Kim, TM, Malik, AB. Transcriptional regulation of endothelial cell and vascular development. Circulation Research. 2013;112(10):1380–1400.CrossRefGoogle ScholarPubMed
Kotch, LE, Iyer, NV, Laughner, E, Semenza, GL. Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Developmental Biology. 1999;209(2):254–267.CrossRefGoogle Scholar
Semenza, GL, Agani, F, Iyer, N, Kotch, L, Laughner, E, Leung, S, et al. Regulation of cardiovascular development and physiology by hypoxia-inducible factor 1. Annals of the New York Academy of Sciences. 1999;874:262–268.CrossRefGoogle ScholarPubMed
Compernolle, V, Brusselmans, K, Acker, T, Hoet, P, Tjwa, M, Beck, H, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nature Medicine. 2002;8(7):702–710.CrossRefGoogle ScholarPubMed
Jones, PL. Homeobox genes in pulmonary vascular development and disease. Trends in Cardiovascular Medicine. 2003;13(8):336–345.CrossRefGoogle ScholarPubMed
Volpe, MV, Ramadurai, SM, Pham, LD, Nielsen, HC. Hoxb-5 down regulation alters Tenascin-C, FGF10 and Hoxb gene expression patterns in pseudoglandular period fetal mouse lung. Frontiers in Bioscience: A Journal and Virtual Library. 2007;12:860–873.CrossRefGoogle ScholarPubMed
Ihida-Stansbury, K, McKean, DM, Gebb, SA, Martin, JF, Stevens, T, Nemenoff, R, et al. Paired-related homeobox gene Prx1 is required for pulmonary vascular development. Circulation Research. 2004;94(11):1507–1514.CrossRefGoogle ScholarPubMed
Lim, L, Kalinichenko, VV, Whitsett, JA, Costa, RH. Fusion of lung lobes and vessels in mouse embryos heterozygous for the forkhead box f1 targeted allele. American Journal of Physiology Lung Cellular and Molecular Physiology. 2002;282(5):L1012–1022.CrossRefGoogle ScholarPubMed
Seo, S, Fujita, H, Nakano, A, Kang, M, Duarte, A, Kume, T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Developmental Biology. 2006;294(2):458–470.CrossRefGoogle ScholarPubMed
Lange, AW, Haitchi, HM, Le Cras, TD, Sridharan, A, Xu, Y, Wert, SE, et al. Sox17 is required for normal pulmonary vascular morphogenesis. Developmental Biology. 2014;387(1):109–120.CrossRefGoogle ScholarPubMed
Minami, T, Murakami, T, Horiuchi, K, Miura, M, Noguchi, T, Miyazaki, J, et al. Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling. The Journal of Biological Chemistry. 2004;279(20):20626–20635.CrossRefGoogle ScholarPubMed
Roman, J, McDonald, JA. Expression of fibronectin, the integrin alpha 5, and alpha-smooth muscle actin in heart and lung development. American Journal of Respiratory Cell and Molecular Biology. 1992;6(5):472–480.CrossRefGoogle ScholarPubMed
Hausladen, JM, Davis, EC, Pierce, RA, Mecham, RP. Formation of the pulmonary vasculature: elastic fiber proteins as markers of cellular differentiation and vascular development. Chest. 1998;114(1 Suppl):6S.CrossRefGoogle ScholarPubMed
Shifren, A, Durmowicz, AG, Knutsen, RH, Faury, G, Mecham, RP. Elastin insufficiency predisposes to elevated pulmonary circulatory pressures through changes in elastic artery structure. Journal of Applied Physiology. 2008;105(5):1610–1619.CrossRefGoogle ScholarPubMed
Albelda, SM. Endothelial and epithelial cell adhesion molecules. American Journal of Respiratory Cell and Molecular Biology. 1991;4(3):195–203.CrossRefGoogle ScholarPubMed
Sheppard, D. Roles of alphav integrins in vascular biology and pulmonary pathology. Current Opinion in Cell Biology. 2004;16(5):552–557.CrossRefGoogle ScholarPubMed
Sen, P, Dharmadhikari, AV, Majewski, T, Mohammad, MA, Kalin, TV, Zabielska, J, et al. Comparative analyses of lung transcriptomes in patients with alveolar capillary dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout mice. PLoS One. 2014;9(4):e94390.CrossRefGoogle ScholarPubMed
You, LR, Takamoto, N, Yu, CT, Tanaka, T, Kodama, T, Demayo, FJ, et al. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(45):16351–16356.CrossRefGoogle ScholarPubMed
Tobin, CE. Human pulmonic lymphatics; an anatomic study. The Anatomical Record. 1957;127(3):611–633.CrossRefGoogle ScholarPubMed
Wigle, JT, Oliver, G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98(6):769–778.CrossRefGoogle ScholarPubMed
Jeltsch, M, Kaipainen, A, Joukov, V, Meng, X, Lakso, M, Rauvala, H, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276(5317):1423–1425.CrossRefGoogle ScholarPubMed
Yao, LC, Testini, C, Tvorogov, D, Anisimov, A, Vargas, SO, Baluk, P, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circulation Research. 2014;114(5):806–822.CrossRefGoogle ScholarPubMed
Baldwin, ME, Halford, MM, Roufail, S, Williams, RA, Hibbs, ML, Grail, D, et al. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Molecular and Cellular Biology. 2005;25(6):2441–2449.CrossRefGoogle ScholarPubMed
Mallory, BP, Mead, TJ, Wiginton, DA, Kulkarni, RM, Greenberg, JM, Akeson, AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvascular Research. 2006;72(1–2):62–73.CrossRefGoogle ScholarPubMed
Wu, X, Liu, NF. FOXC2 transcription factor: a novel regulator of lymphangiogenesis. Lymphology. 2011;44(1):35–41.Google ScholarPubMed
Yoshimatsu, Y, Lee, YG, Akatsu, Y, Taguchi, L, Suzuki, HI, Cunha, SI, et al. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(47):18940–18945.CrossRefGoogle ScholarPubMed
Kulkarni, RM, Greenberg, JM, Akeson, AL. NFATc1 regulates lymphatic endothelial development. Mechanisms of Development. 2009;126(5–6):350–365.CrossRefGoogle ScholarPubMed
Treutlein, B, Brownfield, DG, Wu, AR, Neff, NF, Mantalas, GL, Espinoza, FH, et al. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature. 2014;509(7500):371–375.CrossRefGoogle ScholarPubMed
Bland, RD, Ling, CY, Albertine, KH, Carlton, DP, MacRitchie, AJ, Day, RW, et al. Pulmonary vascular dysfunction in preterm lambs with chronic lung disease. American Journal of Physiology Lung Cellular and Molecular Physiology. 2003;285(1):L76–85.CrossRefGoogle ScholarPubMed
Mokres, LM, Parai, K, Hilgendorff, A, Ertsey, R, Alvira, CM, Rabinovitch, M, et al. Prolonged mechanical ventilation with air induces apoptosis and causes failure of alveolar septation and angiogenesis in lungs of newborn mice. American Journal of Physiology Lung Cellular and Molecular Physiology. 2010;298(1):L23–35.CrossRefGoogle ScholarPubMed
Hilgendorff, A, Parai, K, Ertsey, R, Jain, N, Navarro, EF, Peterson, JL, et al. Inhibiting lung elastase activity enables lung growth in mechanically ventilated newborn mice. American Journal of Respiratory and Critical Care Medicine. 2011;184(5):537–546.CrossRefGoogle ScholarPubMed
Wilson, WL, Mullen, M, Olley, PM, Rabinovitch, M. Hyperoxia-induced pulmonary vascular and lung abnormalities in young rats and potential for recovery. Pediatric Research. 1985;19(10):1059–1067.CrossRefGoogle ScholarPubMed
Rabinovitch, M, Gamble, WJ, Miettinen, OS, Reid, L. Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. The American Journal of Physiology. 1981;240(1):H62–72.Google ScholarPubMed
Koppel, R, Han, RN, Cox, D, Tanswell, AK, Rabinovitch, M. Alpha 1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity. Pediatric Research. 1994;36(6):763–770.CrossRefGoogle ScholarPubMed
Todd, L, Mullen, M, Olley, PM, Rabinovitch, M. Pulmonary toxicity of monocrotaline differs at critical periods of lung development. Pediatric Research. 1985;19(7):731–737.CrossRefGoogle ScholarPubMed
Johnson, RC, Datar, SA, Oishi, PE, Bennett, S, Maki, J, Sun, C, et al. Adaptive right ventricular performance in response to acutely increased afterload in a lamb model of congenital heart disease: evidence for enhanced Anrep effect. American Journal of Physiology Heart and Circulatory Physiology. 2014;306(8):H1222–1230.CrossRefGoogle Scholar
Sharma, S, Aramburo, A, Rafikov, R, Sun, X, Kumar, S, Oishi, PE, et al. L-carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow. Pediatric Research. 2013;74(1):39–47.CrossRefGoogle Scholar
Rabinovitch, M, Keane, JF, Norwood, WI, Castaneda, AR, Reid, L. Vascular structure in lung tissue obtained at biopsy correlated with pulmonary hemodynamic findings after repair of congenital heart defects. Circulation. 1984;69(4):655–667.CrossRefGoogle ScholarPubMed
Haworth, SG, Reid, L. Quantitative structural study of pulmonary circulation in the newborn with pulmonary atresia. Thorax. 1977;32(2):129–133.CrossRefGoogle ScholarPubMed
Haworth, SG, Reid, L. Quantitative structural study of pulmonary circulation in the newborn with aortic atresia, stenosis, or coarctation. Thorax. 1977;32(2):121–128.CrossRefGoogle ScholarPubMed
Haworth, SG. Total anomalous pulmonary venous return. Prenatal damage to pulmonary vascular bed and extrapulmonary veins. British Heart Journal. 1982;48(6):513–524.CrossRefGoogle ScholarPubMed
Fung, ME, Thebaud, B. Stem cell-based therapy for neonatal lung disease: it is in the juice. Pediatric Research. 2014;75(1-1):2–7.CrossRefGoogle ScholarPubMed
Baker, CD, Balasubramaniam, V, Mourani, PM, Sontag, MK, Black, CP, Ryan, SL, et al. Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia. The European Respiratory Journal. 2012;40(6):1516–1522.CrossRefGoogle ScholarPubMed
Alphonse, RS, Vadivel, A, Fung, M, Shelley, WC, Critser, PJ, Ionescu, L, et al. Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth. Circulation. 2014;129(21):2144–2157.CrossRefGoogle ScholarPubMed
Lee, C, Mitsialis, SA, Aslam, M, Vitali, SH, Vergadi, E, Konstantinou, G, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126(22):2601–2611.CrossRefGoogle ScholarPubMed
Fernandez, LG, Le Cras, TD, Ruiz, M, Glover, DK, Kron, IL, Laubach, VE. Differential vascular growth in postpneumonectomy compensatory lung growth. The Journal of Thoracic and Cardiovascular Surgery. 2007;133(2):309–316.CrossRefGoogle ScholarPubMed
Chamoto, K, Gibney, BC, Ackermann, M, Lee, GS, Lin, M, Konerding, MA, et al. Alveolar macrophage dynamics in murine lung regeneration. Journal of Cellular Physiology. 2012;227(9):3208–2115.CrossRefGoogle ScholarPubMed
Ackermann, M, Houdek, JP, Gibney, BC, Ysasi, A, Wagner, W, Belle, J, et al. Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization. Angiogenesis. 2014;17(3):541–551.CrossRefGoogle ScholarPubMed
Dane, DM, Yilmaz, C, Estrera, AS, Hsia, CC. Separating in vivo mechanical stimuli for postpneumonectomy compensation: physiological assessment. Journal of Applied Physiology. 2013;114(1):99–106.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×