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Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy

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Abstract

During pregnancy, trophoblasts invade and transform the maternal spiral arteries that supply blood to the placenta. Recent work has revealed that this process occurs in several stages, and details of the molecular and cellular mechanisms are beginning to emerge, including changes that precede or accompany trophoblastic colonization of the vascular media. Disruption and eventual loss of smooth muscle cells and their associated extracellular matrix are central to physiological transformation. Advances in understanding will lead to the identification of the causative factors involved in failure of remodeling in pathological pregnancies and suggest novel diagnostic and therapeutic avenues.

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References

  1. Craven CM, Morgan T., Ward K. Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts. Placenta. 1998;19(4):241–252.

    Article  CAS  PubMed  Google Scholar 

  2. Aplin JD Implantation, trophoblast differentiation and haemochorial placentation: mechanistic evidence in vivo and in vitro. J Cell Sci. 1991;99(pt 4):681–692.

    PubMed  Google Scholar 

  3. Pijnenborg R., Vercruysse L., Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006;27(9–10):939–958.

    Article  CAS  PubMed  Google Scholar 

  4. Ball E., Bulmer JN, Ayis S, et al. Late sporadic miscarriage is associated with abnormalities in spiral artery transformation and trophoblast invasion. J Pathol. 2006;208(4):535–542.

    Article  CAS  PubMed  Google Scholar 

  5. Kim YM, Bujold E., Chaiworapongsa T, et al. Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2003;189(4):1063–1069.

    Article  PubMed  Google Scholar 

  6. Allt G., Lawrenson JG Pericytes: cell biology and pathology. Cells Tissues Organs. 2001;169(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  7. Alimohamad H., Habijanac T., Larjava H, et al. Colocalization of the collagen-binding proteoglycans decorin, biglycan, fibromodulin and lumican with different cells in human gingiva. J Periodontal Res. 2005;40(1):73–86.

    Article  CAS  PubMed  Google Scholar 

  8. Canfield AE, Allen TD, Grant ME, et al. Modulation of extracellular matrix biosynthesis by bovine retinal pericytes in vitro: effects of the substratum and cell density. J Cell Sci. 1990;96(pt 1):159–169.

    CAS  PubMed  Google Scholar 

  9. Schor AM, Canfield AE, Sutton AB, et al. Pericyte differentiation. Clin Orthop Relat Res. 1995;(313):81–91.

    Google Scholar 

  10. Myllyharju J., Kivirikko KI Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet. 2004;20(1):33–43.

    Article  CAS  PubMed  Google Scholar 

  11. Shekhonin BV, Domogatsky SP, Muzykantov VR, et al. Distribution of type I, III, IV and V collagen in normal and atherosclerotic human arterial wall: immunomorphological characteristics. Coll Relat Res. 1985;5(4):355–368.

    Article  CAS  PubMed  Google Scholar 

  12. Jacob MP Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother. 2003;57(5–6): 195–202.

    Article  CAS  PubMed  Google Scholar 

  13. Zanetti M., Braghetta P., Sabatelli P, et al. EMILIN-1 deficiency induces elastogenesis and vascular cell defects. Mol Cell Biol. 2004;24(2):638–650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Spessotto P., Bulla R., Danussi C, et al. EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall. J Cell Sci. 2006;119(pt 21): 4574–4584.

    Article  CAS  PubMed  Google Scholar 

  15. Heissig B., Hattori K., Friedrich M, et al. Angiogenesis: vascular remodeling of the extracellular matrix involves metalloproteinases. Curr Opin Hematol. 2003;10(2):136–141.

    Article  CAS  PubMed  Google Scholar 

  16. Pepper MS Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol. 2001;21(7):1104–1117.

    Article  CAS  PubMed  Google Scholar 

  17. Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol. 2004;16(5):558–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Davis GE, Bayless KJ, Mavila A. Molecular basis of endothelial cell morphogenesis in three-dimensional extracellular matrices. Anat Rec. 2002;268(3):252–275.

    Article  CAS  PubMed  Google Scholar 

  19. McGuire JK, Li Q., Parks WC Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol. 2003; 162(6):1831–1843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Covington MD, Bayless KJ, Burghardt RC, et al. Ischemia-induced cleavage of cadherins in NRK cells: evidence for a role of metalloproteinases. Am J Physiol Renal Physiol. 2005; 289(2):F280–F288.

    Article  CAS  PubMed  Google Scholar 

  21. Ham C., Levkau B., Raines EW, et al. ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin. Exp Cell Res. 2002;279(2):239–247.

    Article  CAS  PubMed  Google Scholar 

  22. Horiuchi K., Weskamp G., Lum L, et al. Potential role for ADAM15 in pathological neovascularization in mice. Mol Cell Biol. 2003;23(16):5614–5624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bazzoni G., Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869–901.

    Article  CAS  PubMed  Google Scholar 

  24. Dejana E. Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol. 2004;5(4):261–270.

    Article  CAS  PubMed  Google Scholar 

  25. Nawrocki B., Polette M., Marchand V, et al. Membrane-type matrix metalloproteinase-1 expression at the site of human placentation. Placenta. 1996;17(8):565–572.

    Article  CAS  PubMed  Google Scholar 

  26. Vegh GL, Selcuk Tuncer Z, Fulop V, et al. Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta. Gynecol Oncol. 1999;75(2):248–253.

    Article  CAS  PubMed  Google Scholar 

  27. Lash GE, Otun HA, Innes BA, et al. Interferon-gamma inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels. FASEB J. 2006;20(14):2512–2518.

    Article  CAS  PubMed  Google Scholar 

  28. Librach CL, Feigenbaum SL, Bass KE, et al. Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasion in vitro. J Biol Chem. 1994;269(25):17125–17131.

    CAS  PubMed  Google Scholar 

  29. Librach CL, Werb Z., Fitzgerald ML, et al. 92-kD type IV collagenase mediates invasion of human cytotrophoblasts. J Cell Biol. 1991;113(2):437–449.

    Article  CAS  PubMed  Google Scholar 

  30. Levy BI, Benessiano J., Poitevin P, et al. Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR: role of angiotensin converting enzyme inhibition. Circ Res. 1990;66(2):321–328.

    Article  CAS  PubMed  Google Scholar 

  31. Safar M., Chamiot-Clerc P., Dagher G, et al. Pulse pressure, endothelium function, and arterial stiffness in spontaneously hypertensive rats. Hypertension. 2001;38(6):1416–1421.

    Article  CAS  PubMed  Google Scholar 

  32. Yamamoto K., Yamamoto M., Yamamoto N, et al. Regulation of differentiated properties of vascular smooth muscle cells in atherosclerosis: role of extracellular matrix. Connect Tissue. 2002;34:317–325.

    CAS  Google Scholar 

  33. Harris LK, Keogh RJ, Wareing M, et al. Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a fas ligand-dependent mechanism. Am J Pathol. 2006;169(5):1863–1874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Keogh RJ, Harris LK, Freeman A, et al. Fetal-derived trophoblast utilize the apoptotic cytokine TNF-related apoptosis-inducing ligand (TRAIL) to induce smooth muscle cell death. Circ Res. 2007;100(6):834–841.

    Article  CAS  PubMed  Google Scholar 

  35. Nichols WW Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms. Am J Hypertens. 2005;18(1 pt 2):3S–10S.

    Article  PubMed  Google Scholar 

  36. Houghton AM, Quintero PA, Perkins DL, et al. Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest. 2006;116(3):753–759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hinek A. Nature and the multiple functions of the 67-kD elastin-/laminin binding protein. Cell Adhes Commun. 1994; 2(3):185–193.

    Article  CAS  PubMed  Google Scholar 

  38. Mochizuki S., Brassart B., Hinek A. Signaling pathways transduced through the elastin receptor facilitate proliferation of arterial smooth muscle cells. J Biol Chem. 2002;277(47): 44854–44863.

    Article  CAS  PubMed  Google Scholar 

  39. Varga Z., Jacob MP, Csongor J, et al. Altered phosphatidylinositol breakdown after K-elastin stimulation in PMNLs of elderly. Mech Ageing Dev. 1990; 52(1):61–70.

    Article  CAS  PubMed  Google Scholar 

  40. Faury G. Role of the elastin-laminin receptor in the cardiovascular system. Pathol Biol (Paris). 1998;46(7):517–526.

    CAS  Google Scholar 

  41. Faury G., Ristori MT, Verdetti J., et al. Effect of elastin peptides on vascular tone. J Vasc Res. 1995;32(2):112–119.

    Article  CAS  PubMed  Google Scholar 

  42. Hinek A., Molossi S., Rabinovitch M. Functional interplay between interleukin-1 receptor and elastin binding protein regulates fibronectin production in coronary artery smooth muscle cells. Exp Cell Res. 1996;225(1):122–131.

    Article  CAS  PubMed  Google Scholar 

  43. Ntayi C., Labrousse AL, Debret R, et al. Elastin-derived peptides upregulate matrix metalloproteinase-2-mediated melanoma cell invasion through elastin-binding protein. J Invest Dermatol. 2004;122(2):256–265.

    Article  CAS  PubMed  Google Scholar 

  44. Brassart B., Randoux A., Hornebeck W, et al. Regulation of matrix metalloproteinase-2 (gelatinase A, MMP-2), membrane-type matrix metalloproteinase-1 (MT1-MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line. Clin Exp Metastasis. 1998;16(6):489–500.

    Article  CAS  PubMed  Google Scholar 

  45. Hornebeck W., Derouette JC, Brechemier D, et al. Elastogenesis and elastinolytic activity in human breast cancer. Biomedicine. 1977;26(1):48–52.

    CAS  PubMed  Google Scholar 

  46. Host NB, Hansen SS, Jensen LT, et al. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism. Cardiology. 1994;85(5):323–333.

    Article  CAS  PubMed  Google Scholar 

  47. Jensen LT, Horslev-Petersen K., Toft P, et al. Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction. Circulation. 1990;81(1):52–57.

    Article  CAS  PubMed  Google Scholar 

  48. Peuhkurinen KJ, Risteli L., Melkko JT, et al. Thrombolytic therapy with streptokinase stimulates collagen breakdown. Circulation. 1991;83(6):1969–1975.

    Article  CAS  PubMed  Google Scholar 

  49. Poulsen SH, Host NB, Egstrup K. Long-term changes in collagen formation expressed by serum carboxyterminal propeptide of type-I procollagen and relation to left ventricular function after acute myocardial infarction. Cardiology. 2001;96(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  50. Sund M., Xie L., Kalluri R. The contribution of vascular basement membranes and extracellular matrix to the mechanics of tumor angiogenesis. Apmis. 2004;112(7–8):450–462.

    Article  CAS  PubMed  Google Scholar 

  51. Shapiro SD Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol. 1998;10(5):602–608.

    Article  CAS  PubMed  Google Scholar 

  52. Ashworth JL, Murphy G., Rock MJ, et al. Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling. Biochem J. 1999;340 (pt 1):171–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kielty CM, Woolley DE, Whittaker SP, et al. Catabolism of intact fibrillin microfibrils by neutrophil elastase, chymotrypsin and trypsin. FEBS Lett. 1994;351(1):85–89.

    Article  CAS  PubMed  Google Scholar 

  54. Rabinovitch M. EVE and beyond, retro and prospective insights. Am J Physiol. 1999;277(1 pt 1):L5–L12.

    CAS  PubMed  Google Scholar 

  55. Cowan KN, Leung WC, Mar C, et al. Caspases from apoptotic myocytes degrade extracellular matrix: a novel remodeling paradigm. FASEB J. 2005; 19(13):1848–1850.

    Article  CAS  PubMed  Google Scholar 

  56. Chapman HA, Riese RJ, Shi GP Emerging roles for cysteine proteases in human biology. Annu Rev Physiol. 1997;59:63–88.

    Article  CAS  PubMed  Google Scholar 

  57. Hornebeck W., Brechemier D., Bourdillon MC, et al. Isolation and partial characterization of an elastase-like protease from rat aorta smooth muscle cells: possible role in the regulation of elastin biosynthesis. Connect Tissue Res. 1981;8(3–4):245–249.

    Article  CAS  PubMed  Google Scholar 

  58. Campbell EJ, Wald MS Hypoxic injury to human alveolar macrophages accelerates release of previously bound neutrophil elastase: implications for lung connective tissue injury including pulmonary emphysema. Am Rev Respir Dis. 1983; 127(5):631–635.

    Article  CAS  PubMed  Google Scholar 

  59. Werb Z., Banda MJ, Jones PA Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages. J Exp Med. 1980;152(5):1340–1357.

    Article  CAS  PubMed  Google Scholar 

  60. Legrand Y., Pignaud G., Caen JP, et al. Separation of human blood platelet elastase and proelastase by affinity chromatography. Biochem Biophys Res Commun. 1975;63(1):224–231.

    Article  CAS  PubMed  Google Scholar 

  61. Yamada E., Hazama F., Kataoka H, et al. Elastase-like enzyme in the aorta of spontaneously hypertensive rats. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;44(2):241–245.

    Article  CAS  PubMed  Google Scholar 

  62. Staun-Ram E., Goldman S., Gabarin D, et al. Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reprod BiolEndocrinol. 2004; 2:59–71.

    Google Scholar 

  63. Nakanishi T., Ozaki Y., Blomgren K, et al. Role of cathepsins and cystatins in patients with recurrent miscarriage. Mol Hum Reprod. 2005;11(5):351–355.

    Article  CAS  PubMed  Google Scholar 

  64. Shipley JM, Doyle GA, Fliszar CJ, et al. The structural basis for the elastolytic activity of the 92-kDa and 72-kDa gelatinases: role of the fibronectin type II-like repeats. J Biol Chem. 1996;271(8):4335–4341.

    Article  CAS  PubMed  Google Scholar 

  65. Sukhova GK, Shi GP, Simon DI, et al. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest. 1998;102(3):576–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Uzui H., Harpf A., Liu M, et al. Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines. Circulation. 2002;106(24):3024–3030.

    Article  CAS  PubMed  Google Scholar 

  67. Dollery CM, Owen CA, Sukhova GK, et al. Neutrophil elastase in human atherosclerotic plaques: production by macrophages. Circulation. 2003;107(22):2829–2836.

    Article  CAS  PubMed  Google Scholar 

  68. Reister F., Frank HG, Heyl W, et al. The distribution of macrophages in spiral arteries of the placental bed in preeclampsia differs from that in healthy patients. Placenta. 1999; 20(2–3):229–233.

    Article  CAS  PubMed  Google Scholar 

  69. Ashkar AA, Di Santo JP, Croy BA. Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med. 2000;192(2):259–270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Esadeg S., He H., Pijnenborg R, et al. Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites. Placenta. 2003;24(10):912–921.

    Article  CAS  PubMed  Google Scholar 

  71. Tchougounova E., Forsberg E., Angelborg G, et al. Altered processing of fibronectin in mice lacking heparin: a role for heparin-dependent mast cell chymase in fibronectin degradation. J Biol Chem. 2001; 276(6):3772–3777.

    Article  CAS  PubMed  Google Scholar 

  72. Kofford MW, Schwartz LB, Schechter NM, et al. Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide. J Biol Chem. 1997;272(11):7127–7131.

    Article  CAS  PubMed  Google Scholar 

  73. Szewczyk G., Szewczyk A., Pyzlak M, et al. Mast cells, histamine and development of the placental vascular network in pregnancies complicated by preeclampsia and intrauterine growth retardation [in Polish]. Ginekol Pol. 2005;76(9):727–734.

    PubMed  Google Scholar 

  74. Noack F., Kruger S., Thorns C, et al. Application of novel tissue microarrays to investigate expression of tryptase, chymase and KIT protein in placental mast cells. Arch Gynecol Obstet. 2005;272(3):223–228.

    Article  CAS  PubMed  Google Scholar 

  75. Mitani R., Maeda K., Fukui R, et al. Production of human mast cell chymase in human myometrium and placenta in cases of normal pregnancy and preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2002;101(2):155–160.

    Article  CAS  PubMed  Google Scholar 

  76. Shapiro RL, Duquette JG, Roses DF, et al. Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. Cancer Res. 1996;56(15):3597–3604.

    CAS  PubMed  Google Scholar 

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Harris, L.K., Aplin, J.D. Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy. Reprod. Sci. 14 (Suppl 8), 28–34 (2007). https://doi.org/10.1177/1933719107309588

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