Angiogenesis and the Expression of Vascular Endothelial Growth Factor in Endometrium and Placenta
Corresponding Author
Dr. Donald S. Torry
Department of OB/GYN, The University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37920
Department of OB/GYN, The University of Tennessee Graduate School of Medicine, Box U-27, 1924 Alcoa Highway, Knoxville, TN 37920.Search for more papers by this authorRonald J. Torry
Division of Experimental Pathology, Center for Reproduction and Transplantation Immunology, Methodist Hospital, Indianapolis, Indiana 46202
Search for more papers by this authorCorresponding Author
Dr. Donald S. Torry
Department of OB/GYN, The University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37920
Department of OB/GYN, The University of Tennessee Graduate School of Medicine, Box U-27, 1924 Alcoa Highway, Knoxville, TN 37920.Search for more papers by this authorRonald J. Torry
Division of Experimental Pathology, Center for Reproduction and Transplantation Immunology, Methodist Hospital, Indianapolis, Indiana 46202
Search for more papers by this authorAbstract
PROBLEM: The demand for increased angiogenesis and microvascular permeability during cyclical changes in the endometrium and during placentation raises the possibility that aberrations in these events could lead to suboptimal reproductive performance. However, relatively little is presently known regarding the regulation of vascular growth and permeability in these tissues.
METHOD OF STUDY: This review of current literature focuses on the expression, regulation, and potential physiological effects of vascular endothelial growth factor (VEGF) within endometrial and placental tissue.
RESULTS: Spatial and temporal expression of VEGF as well as its restricted specificity, essential role in vasculogenesis/angiogenesis, and ability to induce vascular permeability makes VEGF an attractive regulator of vascular growth and permeability in the endometrium and placenta.
CONCLUSION: A better understanding of the production, regulation, and physiological responses of the vasculature to angiogenic growth factors may lead to new therapeutic strategies for reproductive disturbances secondary to vascular insufficiencies within the female reproductive tract.
REFERENCES
- 1
Simpson JG,
Fraser RA,
Thompson WD: Angiogenesis and angiogenesis factors. Prog..
Appl Microcirc
1983; 1: 71–85.
10.1159/000407815 Google Scholar
- 2 Findlay JK: Angiogenesis in reproductive tissues. J Endocrinol 1986; 111: 357–366.
- 3 Tony RJ, Rongish BJ: Angiogenesis in the uterus: Potential regulation and relation to tumor angiogenesis. Am J Reprod Immunol 1992; 27: 171–179.
- 4 Goodger-Macpherson AM, Rogers PAW: Blood vessel growth in the endometrium. Microcirculation 1995; 2: 329–343.
- 5 Reynolds LP, Killilea SD, Remer DA: Angiogenesis in the female reproductive system. FASEB J. 1992; 6: 886–892.
- 6 Clark D.: Cytokines, decidua, and early pregnancy. Oxford Rev Reprod Biol 1993; 15: 83–111.
- 7 Haimovici F., Anderson D.: Cytokines and growth factors in implantation. Microscopy Res Techniq 1993; 25: 201–207.
- 8 McMaster MT, Bass KE, Fisher SJ: Human trophoblast invasion. Autocrine control and paracrine modulation. Ann NY Acad Sci 1994; 734: 122–31.
- 9 Feinberg BB, Anderson DJ, Steller MA, Fulop V., Berkowitz RS, Hill JA: Cytokine regulation of trophoblast steroidogenesis. J Clin Endocrinol Metabol 1994; 78: 586–591.
- 10 Klagsbrun M.: Angiogenesis factors. In Endothelial cells, Vol II. US Ryan (ed). CRC Press, Boca Raton, 1988, pp 38–50.
- 11 Folkman J., Klagsbrun M. Angiogenic factors. Science 1987; 235: 442–446.
- 12
Madri JA,
Pratt BM.
Angiogenesis. In: The molecular and cellular biology of wound repair. RAF Clark and
PM Henson (eds.). Plenum Press, New York, 1988, pp 337–358.
10.1007/978-1-4615-1795-5_15 Google Scholar
- 13
Maragoudakis ME.
The role of basement membrane in angiogenesis. In: Vascular endothelium: Receptors and transduction mechanisms. JD Cravas,
CN Gillis,
US Ryan (eds.). Plenum Press, New York, 1989, pp 111–120.
10.1007/978-1-4684-8532-5_10 Google Scholar
- 14 D'Amore PA, Braunhut SJ. Stimulating and inhibitory factors in vascular growth control. In: Endothelial cells, Vol II. US Ryan (ed). CRC Press, Boca Raton, 1988, pp 13–36.
- 15 D'Amore P., Thompson R. Mechanisms of angiogenesis. Annu Rev Physiol 1987; 49: 453–464.
- 16 Giudice LC. Growth factors and growth modulators in human uterine endometrium: Their potential relevance to reproductive medicine. Fertil Steril 1994; 61: 1–17.
- 17 Neufeld G., Tessler S., Gitay-Goren H., Cohen T., Levi BZ. Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 1994; 5: 89–97.
- 18 Ferrara N., Houck KA, Jakeman LB, Winer J., Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem 1991; 47: 211–218.
- 19 Houck, KA, Leung, DW, Rowland AM, Winer J., Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992; 267: 26031–26037.
- 20 Bikfalvi A., Sauzeau C., Moukadiri H., Maclouf J., Busso N., Bryckaert M., Plouet J., Tobelem G. Interaction of vasculotropin/vascular endothelial cell growth factor with human umbilical vein endothelial cells: Binding, internalization, degradation, and biological effects. J Cell Physiol 1991; 149: 50–59.
- 21 Wilting J., Christ B., Bokeloh M., Weich HA. In vivo effects of vascular endothelial growth factor on the chicken chorioallantoic membrane. Cell Tissue Res 1993; 274: 163–172.
- 22 Senger DR, Connolly DT, Van de Water L., Feder J., Dvorak HF: Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res 1990; 50: 1774–1778.
- 23 De Vries C., Escobedo JA, Ueno H., Houck K., Ferrara N., Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992; 255: 989–991.
- 24 Terman BI, Dougher-Vermazen M., Carrion ME, Dimitrov D., Armellino DC, Gospodarowicz D., Bohlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Comm 1992; 187: 1579–1586.
- 25 Jakeman LB, Winer J., Bennett GL, Altar CA, Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992; 89: 244–253.
- 26 Holt VJ, Wang T-H, Wang C-L, Torry RJ, Caudle MR, Torry DT. Characterization of vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast. (submitted) 1996.
- 27 Charnock-Jones DS, Sharkey AM, Rajput-Williams J., Burch D., Schofield JP, Fountain SA, Boocock CA, Smith SK. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells. Biol Reprod 1994; 51: 524–530.
- 28 Carmeliet P., Ferreira V., Breier G., Pollefeyt S., Kieckens L., Gertsenstein M., Fahrig M., Vandenhoeck A., Harpal K., Eberhardt C., Declercq C., Pawling J., Moons L., Collen D., Risau W., Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435–439.
- 29 Ferrara N., Carver-Moore K., Chen H., Dowd M., Lu L., O'Shea KS, Powell-Braxton L., Hillian KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439–442.
- 30 Kim KJ, Li B., Houck K., Winer J., Ferrara N. The vascular endothelial growth factor proteins: Identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors 1992; 7: 53–64.
- 31 Millauer B., Shawver LK, Plate KH, Risau W., Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 1994; 367: 576–579.
- 32 Saleh M., Stacker SA, Wilks AF. Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res 1996; 56: 393–401.
- 33 Folkman J. Tumor angiogenesis. Adv Cancer Res 1985; 43: 175–203.
- 34 Denekamp J. Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev 1990; 9: 267–282.
- 35 Fong GH, Rossant J., Gertsenstein M., Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376: 66–70.
- 36 Shalaby F., Rossant J., Yamaguchi TP, Gertsenstein M., Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376: 62–66.
- 37 Torry DT, Holt VJ, Keenan JA, Harris GA, Caudle MR, Torry RT. Vascular endothelial cell growth factor (VEGF) expression in cycling human endometrium. Fertil Steril 1996; 66: 72–80.
- 38 Li XF, Gregory J., Ahmed A. Immunolocalisation of vascular endothelial growth factor in human endometrium. Growth Factors 1994; 11: 277–282.
- 39 Shifren JL, Tseng JF, Zaloudek CJ, Ryan IP, Meng YG, Ferrara N., Jaffe RB, Taylor RN. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: Implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis. J Clin Endocrinol Metabol 1996; 81: 3112–3118.
- 40 Greb, RR, Bukowski R., Hsiu JG, Williams RF, Hodgen GD, Goodman AL. Vascular endothelial growth factor (VEGF) in primate endometrium: Immunohistochemical patterns during the cycle and after chronic RU 486 treatment in cynomolgus monkeys. Ann NY Acad Sci 1995; 761: 376–381.
- 41 Charnock-Jones DS, Sharkey AM, Rajput-Williams J., Burch D., Schofield JP, Fountain SA, Boocock CK, Smith SK. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod 1993; 48: 1120–1128.
- 42 Cullinan-Bove K., Koos RD. Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: Rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology 1993; 133: 829–837.
- 43 Harrison-Woolrych ML, Sharkey AM, Charnock-Jones DS, Smith SK. Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol Metab 1995; 80: 1853–1858.
- 44 Shweiki D., Itin A., Neufeld G., Gitay-Goren H., Keshet E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993; 91: 2235–2243.
- 45 Li J., Perrella MA, Tsai JC, Yet SF, Hsieh CM, Yoshizumi M., Patterson C., Endege WO, Zhou F., Lee ME. Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells. J Biol Chem 1995; 270: 308–312.
- 46 Goldman CK, Kim J., Wong WL, King V., Brock T., Gillespie GY. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: A model of glioblastoma multiforme pathophysiology. Mol Biol Cell 1993; 4: 121–133.
- 47 Pepper MS, Vassalli JD, Orci L., Montesano R. Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis. Exp Cell Res 1993; 204: 356–363.
- 48 Brogi E., Wu T., Namiki A., Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation 1994; 90: 649–652.
- 49 Goldberg MA, Schneider TJ. Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem 1994; 269: 4355–4359.
- 50 Torry RJ, Labarrere CA, Holt VJ, Torry DT, Faulk WP. Expression of vascular endothelial growth factor in transplanted human hearts. Transplantation 1995; 60: 1451–1457.
- 51 Goodger-Macpherson AM, Rogers PAW. Endometrial endothelial cell proliferation during the menstrual cycle. Human Reprod 1994; 9: 399–405.
- 52 Iruela-Arispe ML, Porter P., Bornstein P., Sage EH. Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium. J Clin Invest 1996; 97: 403–412.
- 53 Dvorak HF, Senger DR, Dvorak AM, Harvey VS, McDonagh J. Regulation of extravascular coagulation by microvascular permeability. Science 1985; 227: 1057.
- 54 Dvorak HF, Brown LF, Detmar M., Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146: 1029–1039.
- 55 Kamat BR, Brown LF, Manseau EJ, Senger DR, Dvorak HF. Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells: Role in corpus luteum development. Am J Pathol 1995; 146: 157–165.
- 56 Ramey JW, Archer DF: Peritoneal fluid: Its relevance to the development of endometriosis. Fertil Steril 1993; 60: 1–14.
- 57 Oosterlynck DJ, Meuleman C., Sobis H., Vandeputte M., Kininckx PR. Angiogenic activity of perotineal fluid from women with endometriosis. Fertil Steril 1993; 59: 778–782.
- 58 McLaren J., Prentice A., Charnock-Jones DS, Smith SK. Vascular endothelial growth-factor (VEGF) concentrations are elevated in peritoneal-fluid of women with endometriosis. Hum Reprod 1996; 11: 220–223.
- 59 McLaren J., Prentice A., Charnock-Jones DS, Millican SA, Muller KH, Sharkey AM, Smith SK. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest 1996; 98: 482–489.
- 60 Krasnow JS, Berga SL, Guzick DS, Zeleznik AJ, Yeo KY. Vascular-permeability factor and vascular endothelial growth factor in ovarian hyperstimulation syndrome: A preliminary report. Fertil Steril 1996; 65: 552–555.
- 61 McClure N., Healy DL, Rogers PA, Sullivan J., Beaton L., Haning RV, Connolly DT, Robertson DM. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet 1994; 344: 235–236.
- 62 Jackson, MR, Carney EW, Lye SJ, Ritchie JW. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 1994; 15: 341–353.
- 63 Clark DE, Smith SK, Sharkey AM, Charnock-Jones DS. Localization of VEGF and expression of its receptors flt and KDR in human placenta throughout pregnancy. Hum Reprod 1996; 11: 1090–1098.
- 64 Ahmed A., Li XF, Dunk C., Whittle MJ, Rushton DI, Rollason T.: Colocalisation of vascular endothelial growth factor and its Flt-1 receptor in human placenta. Growth Factors 1995; 12: 235–243.
- 65 Shiraishi S., Nakagawa K., Kinukawa N., Nakano H., Sueishi K. Immunohistochemical localization of vascular endothelial growth-factor in the human placenta. Placenta 1996; 17: 111–121.
- 66 Sharkey AM, Charnock-Jones DS, Boocock CA, Brown KD, Smith S. Expression of mRNA for vascular endothelial growth factor in human placenta. J Reprod Fertil 1993; 99: 609–615.
- 67 Shen H., Clauss M., Ryan J., Schmidt AM, Tijburg P., Borden L., Connolly D., Stern D., Kao J.: Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. Blood 1993; 81: 2767–2773.
- 68 Hatva E., Kaipainen A., Mentula P., Jaaskelainen J., Paetau A., Haltia M., Alitalo K. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am J Pathol 1995; 146: 368–378.
- 69 Boocock CA, Charnock-Jones DS, Sharkey AM, McLaren J., Barker PJ, Wright KA, Twentyman PR, Smith SK. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst 1995; 87: 506–516.
- 70 Vuckovic M., Ponting J., Terman BI, Niketic V., Seif MW, Kumar S. Expression of the vascular endothelial growth-factor receptor, KDR, in human placenta. J Anat 1996; 188: 361–366.
- 71 Athanassiades A., Hamilton GS, Lala PK. Vascular endothelial growth factor (VEGF) provides an autocrine signal for first trimester extravillous trophoblast cell proliferation. Biol Reprod 1996; 54: 130.
- 72 Millauer B., Wizigmann-Voos S., Schnurch H., Martinez R., Moller NP, Risau W., Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 1993; 72: 835–846.
- 73 Adair TH, Gay WJ, Montani JP. Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 1990; 259(Regulatory Integrative Comp. Physiology 28): R393–404.
- 74 Ladoux A., Frelin C. Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart. Biochem Biophys Res Comm 1993; 195: 1005–1010.
- 75 Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843–845.
- 76 Wheeler T., Elcock CL, Anthony FW. Angiogenesis and the placental environment. Placenta 1995; 16: 289–296.
- 77 Finkenzeller G., Marme D., Weich HA, Hug H. Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C. Cancer Research 1992; 52: 4821–4823.
- 78 Stavri G T, Hong Y., Zachary IC, Breier G., Baskerville PA, Yla-Herttuala S., Risau W., Martin JF, Erusalimsky JD. Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells. Febs Lett 1995; 358: 311–315.
- 79 Friedman SA, Taylor RN, Roberts JN. Pathophysiology of Preeclampsia. In: Clinics in perinatology. BM Sibai (ed). 1991, Vol 18, pp 661–682.
- 80 De Groot CJ, Taylor RN. New insights into the etiology of pre-eclampsia. Ann Med 1993; 25: 243–249.
- 81 Genbacev O., Joslin R., Damsky CH, Polliotti BM, Fisher SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 1996; 97: 540–550.
- 82 Clauss M., Gerlach M., Gerlach H., Brett J., Wang F., Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D.: Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535–1545.
- 83 Baker PN, Krasnow J., Roberts JM, Yeo KT. Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia. Obstet Gynecol 1995; 86: 815–821.
- 84 Tapanainen PJ, Bang P., Wilson K., Unterman TG, Vreman HJ, Rosenfeld RG: Maternal hypoxia as a model for intrauterine growth retardation: effects on insulin-like growth factors and their binding proteins. Pediatr Res 1994; 36: 152–158.
- 85 Tanaka M., Natori M., Ishimoto H., Miyazaki T., Kobayashi T., Nozawa S. Experimental growth retardation produced by transient period of uteroplacental ischemia in pregnant Sprague-Dawley rats. Am J Obstet Gynecol 1994; 171: 1231–1234.
- 86 Hoogland HJ, De Haan J., Martin CB. Placental size during early pregnancy and fetal outcome: A preliminary report of a sequential ultrasonographic study. Am J Obstet Gynecol 1980; 138: 441.
- 87 Barker DJ. The fetal and infant origins of disease. Eur J Clin Invest 1995; 25: 457–463.