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Cited by 354Pregnancy and preeclampsia studiesReproductive System and PregnancyNeurological Complications and Syndromes

Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia

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Staff, Anne Cathrine, Fjeldstad, Heidi E., Fosheim, Ingrid Knutsdotter, Moe, Kjartan, Turowski, Gitta, Johnsen, Guro Mørk, Alnaes-Katjavivi, Patji, Sugulle, Meryam·2022·American Journal of Obstetrics and Gynecology
DOI 10.1016/j.ajog.2020.09.026
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Abstract

Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.

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  • As non-transformed arteries still constrict in response to vaso-constricting signals, there is a risk of ischemia-reperfusion damage to the villi.

    “As the non-transformed arteries still constrict in response to vaso-constricting signals, there is also a risk of ischemia-reperfusion damage to the villi (Staff et al., 2022).”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Staff et al., 2022

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Research works printed but not linked: 92

  1. Boyd JD, Hamilton WJ. The human placenta. Cambridge, England: Heffner & Sons Ltd; 1970: 253-66.
  2. Lyall F. The human placental bed revisited. Placenta 2002;23:555-62.
  3. Brosens I, Benagiano M, Puttemans P, D'Elios MM, Benagiano G. The placental bed vascular pathology revisited: a risk indicator for cardiovascular disease. J Matern Fetal Neonatal Med 2019;32:1556-64.
  4. Burton GJ, Woods AW, Jauniaux E, Kingdom JC. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow dur- ing human pregnancy. Placenta 2009;30: 473-82.
  5. Espinoza J, Romero R, Mee Kim Y, et al. Normal and abnormal transformation of the spiral arteries during pregnancy. J Perinat Med 2006;34:447-58.
  6. Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 1967;93:569-79.
  7. Harris LK, Benagiano M, D'Elios MM, Brosens I, Benagiano G. Placental bed research: II. Functional and immunological investigations of the placental bed. Am J Obstet Gynecol 2019;221:457-69.
  8. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 2006;27: 939-58.
  9. Burton GJ, Watson AL, Hempstock J, Skepper JN, Jauniaux E. Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy. J Clin Endocrinol Metab 2002;87:2954-9.
  10. Red-Horse K, Zhou Y, Genbacev O, et al. Trophoblast differentiation during embryo im- plantation and formation of the maternal-fetal interface. J Clin Invest 2004;114:744-54.
  11. Jauniaux E, Poston L, Burton GJ. Placental-related diseases of pregnancy: involvement of oxidative stress and implica- tions in human evolution. Hum Reprod Update 2006;12:747-55.
  12. Craven CM, Morgan T, Ward K. Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts. Placenta 1998;19:241-52.
  13. King A, Loke YW. Placental vascular remodelling. Lancet 1997;350:220-1.
  14. Burton GJ, Charnock-Jones DS, Jauniaux E. Regulation of vascular growth and function in human placenta. Reproduction 2009;138:895-902.
  15. Staff AC. The two-stage placental model of preeclampsia: an update. J Reprod Immunol 2019;134(5):1-10.
  16. Robson A, Harris LK, Innes BA, et al. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB J 2012;26: 4876-85.
  17. Nakimuli A, Chazara O, Hiby SE, et al. A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre- eclampsia. Proc Natl Acad Sci U S A 2015;112: 845-50.
  18. Hiby SE, Apps R, Chazara O, et al. Maternal KIR in combination with paternal HLA-C2 regu- late human birth weight. J Immunol 2014;192: 5069-73.
  19. Tilburgs T, Scherjon SA, van der Mast BJ, et al. Fetal-maternal HLA-C mismatch is asso- ciated with decidual T cell activation and induc- tion of functional T regulatory cells. J Reprod Immunol 2009;82:148-57.
  20. Robertson SA, Care AS, Moldenhauer LM. Regulatory T cells in embryo implantation and the immune response to pregnancy. J Clin Invest 2018;128:4224-35.
  21. Przybyl L, Ibrahim T, Haase N, et al. Regu- latory T cells ameliorate intrauterine growth retardation in a transgenic rat model for pre- eclampsia. Hypertension 2015;65:1298-306.
  22. Care AS, Bourque SL, Morton JS, Hjartarson EP, Robertson SA, Davidge ST. Reduction in regulatory T cells in early pregnancy causes uterine artery dysfunction in mice. Hy- pertension 2018;72:177-87.
  23. Rowe JH, Ertelt JM, Xin L, Way SS. Preg- nancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 2012;490:102-6.
  24. Gamliel M, Goldman-Wohl D, Isaacson B, et al. Trained memory of human uterine NK cells enhances their function in subsequent preg- nancies. Immunity 2018;48:951-62.e5.
  25. Skjærven R, Wilcox AJ, Lie RT. The interval between pregnancies and the risk of pre- eclampsia. N Engl J Med 2002;346:33-8.
  26. Robertson WB, Brosens I, Dixon HG. The pathological response of the vessels of the placental bed to hypertensive pregnancy. J Pathol Bacteriol 1967;93:581-92.
  27. Pijnenborg R, Bland JM, Robertson WB, Brosens I. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta 1983;4: 397-413.
  28. Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in pre- eclampsia and fetal growth restriction: relation- ship to clinical outcome. Hypertension 2013;62: 1046-54.
  29. Labarrere CA, DiCarlo HL, Bammerlin E, et al. Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta. Am J Obstet Gynecol 2017;216: 287.e1-16.
  30. Meekins JW, Pijnenborg R, Hanssens M, McFadyen IR, van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994;101:669-74.
  31. Alnaes-Katjavivi P, Lyall F, Roald B, Redman CW, Staff AC. Acute atherosis in vac- uum suction biopsies of decidua basalis: an evidence based research definition. Placenta 2016;37:26-33.
  32. Fosheim IK, Alnaes-Katjavivi P, Redman C, Roald B, Staff AC, Størvold GL. Acute atherosis of decidua basalis; characterization of spiral ar- teries, endothelial status and activation. Placenta 2019;82:10-6.
  33. Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. Obstet Gynecol Annu 1972;1: 177-91.
  34. Zhou Y, Fisher SJ, Janatpour M, et al. Hu- man cytotrophoblasts adopt a vascular pheno- type as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 1997;99:2139-51.
  35. Zhou Y, Damsky CH, Fisher SJ. Pre- eclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? J Clin Invest 1997;99:2152-64.
  36. Labarrere CA, Faulk WP. Antigenic identifi- cation of cells in spiral artery trophoblastic inva- sion: validation of histologic studies by triple- antibody immunocytochemistry. Am J Obstet Gynecol 1994;171:165-71.
  37. Lyall F, Bulmer JN, Duffie E, Cousins F, Theriault A, Robson SC. Human trophoblast invasion and spiral artery transformation. Am J Pathol 2001;158:1713-21.
  38. Roberts JM, Redman CW. Pre-eclampsia: more Than pregnancy-induced hypertension. Lancet 1993;341:1447-51.
  39. Redman CW, Sacks GP, Sargent IL. Pre- eclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499-506.
  40. Brosens I, Puttemans P, Benagiano G. Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes. Am J Obstet Gynecol 2019;221:437-56.
  41. Avagliano L, Bulfamante GP, Morabito A, Marconi AM. Abnormal spiral artery remodelling in the decidual segment during pregnancy: from histology to clinical correlation. J Clin Pathol 2011;64:1064-8.
  42. Rabaglino MB, Post Uiterweer ED, Jeyabalan A, Hogge WA, Conrad KP. Bioinfor- matics approach reveals evidence for impaired endometrial maturation before and during early pregnancy in women who developed pre- eclampsia. Hypertension 2015;65:421-9.
  43. Moser G, Windsperger K, Pollheimer J, de Sousa Lopes SC, Huppertz B. Human tropho- blast invasion: new and unexpected routes and functions. Histochem Cell Biol 2018;150: 361-70.
  44. Moser G, Weiss G, Sundl M, et al. Extra- villous trophoblasts invade more than uterine arteries: evidence for the invasion of uterine veins. Histochem Cell Biol 2017;147:353-66.
  45. Windsperger K, Dekan S, Pils S, et al. Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions. Hum Reprod 2017;32:1208-17.
  46. Egeland GM, Klungsøyr K, Øyen N, Tell GS, Næss Ø, Skjærven R. Preconception cardio- vascular risk factor differences between gesta- tional hypertension and preeclampsia: cohort Norway study. Hypertension 2016;67:1173-80.
  47. Strøm-Roum EM, Tanbo TG, Eskild A. The associations of maternal body mass index with birthweight and placental weight. Does maternal diabetes matter? A population study of 106 191 pregnancies. Acta Obstet Gynecol Scand 2016;95:1162-70.
  48. Redman CW. Current topic: pre-eclampsia and the placenta. Placenta 1991;12:301-8.
  49. Hertig AT. Vascular pathology in the hyper- tensive albuminuric toxemias of pregnancy. Clinics 1945;4:602-14.
  50. Zeek PM, Assali NS. Vascular changes in the decidua associated with eclamptogenic toxemia of pregnancy. Am J Clin Pathol 1950;20:1099-109.
  51. Meekins JW, Pijnenborg R, Hanssens M, van Assche A, McFadyen IR. Immunohisto- chemical detection of lipoprotein(a) in the wall of placental bed spiral arteries in normal and severe preeclamptic pregnancies. Placenta 1994;15: 511-24.
  52. Robertson WB, Brosens I, Dixon G. Utero- placental vascular pathology. Eur J Obstet Gynecol Reprod Biol 1975;5:47-65.
  53. Alnaes-Katjavivi P, Roald B, Staff AC. Ute- roplacental acute atherosis in preeclamptic pregnancies: rates and clinical outcomes differ by tissue collection methods. Pregnancy Hypertens 2020;19:11-7.
  54. Nayar R, Lage JM. Placental changes in a first trimester missed abortion in maternal sys- temic lupus erythematosus with anti- phospholipid syndrome; a case report and review of the literature. Hum Pathol 1996;27: 201-6.
  55. Kim YM, Chaemsaithong P, Romero R, et al. The frequency of acute atherosis in normal pregnancy and preterm labor, preeclampsia, small-for-gestational age, fetal death and mid- trimester spontaneous abortion. J Matern Fetal Neonatal Med 2015;28:2001-9.
  56. Stevens DU, Al-Nasiry S, Bulten J, Spaanderman ME. Decidual vasculopathy and adverse perinatal outcome in preeclamptic pregnancy. Placenta 2012;33:630-3.
  57. Harsem NK, Roald B, Braekke K, Staff AC. Acute atherosis in decidual tissue: not associated with systemic oxidative stress in preeclampsia. Placenta 2007;28: 958-64.
  58. Khong TY. Acute atherosis in pregnancies complicated by hypertension, small-for- gestational-age infants, and diabetes mellitus. Arch Pathol Lab Med 1991;115:722-5.
  59. Staff AC, Dechend R, Pijnenborg R. Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia- novel aspects for atherosclerosis and future cardiovascular health. Hypertension 2010;56: 1026-34.
  60. Katabuchi H, Yih S, Ohba T, et al. Charac- terization of macrophages in the decidual athe- rotic spiral artery with special reference to the cytology of foam cells. Med Electron Microsc 2003;36:253-62.
  61. Brosens I. How the role of the spiral arteries in the pathogenesis of preeclampsia was ajog.org Expert Review MONTH 2020 American Journal of Obstetrics & Gynecology 11 discovered. Hypertens Pregnancy 1996;15: 143-6.
  62. Harsem NK, Staff AC, He L, Roald B. The decidual suction method: a new way of collect- ing decidual tissue for functional and morpho- logical studies. Acta Obstet Gynecol Scand 2004;83:724-30.
  63. Staff AC, Halvorsen B, Ranheim T, Henriksen T. Elevated level of free 8-iso-pros- taglandin F2alpha in the decidua basalis of women with preeclampsia. Am J Obstet Gyne- col 1999;181:1211-5.
  64. Staff AC, Ranheim T, Khoury J, Henriksen T. Increased contents of phospholipids, choles- terol, and lipid peroxides in decidua basalis in women with preeclampsia. Am J Obstet Gyne- col 1999;180:587-92.
  65. Burton GJ, Sebire NJ, Myatt L, et al. Opti- mising sample collection for placental research. Placenta 2014;35:9-22.
  66. Stevens DU, Al-Nasiry S, Bulten J, Spaanderman ME. Decidual vasculopathy in preeclampsia: lesion characteristics relate to disease severity and perinatal outcome. Placenta 2013;34:805-9.
  67. Johnsen GM, Størvold GL, Alnaes- Katjavivi PH, et al. Lymphocyte characterization of decidua basalis spiral arteries with acute atherosis in preeclamptic and normotensive pregnancies. J Reprod Immunol 2019;132:42-8.
  68. Allahverdian S, Chehroudi AC, McManus BM, Abraham T, Francis GA. Contri- bution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation 2014;129:1551-9.
  69. Staff AC, Dechend R, Redman CW. Review: preeclampsia, acute atherosis of the spiral ar- teries and future cardiovascular disease: two new hypotheses. Placenta 2013;34(Suppl):S73-8.
  70. Libby P, Hansson GK. Inflammation and immunity in diseases of the arterial tree: players and layers. Circ Res 2015;116:307-11.
  71. Redman CW. Immunological aspects of pre-eclampsia. Baillieres Clin Obstet Gynaecol 1992;6:601-15.
  72. Maqueo M, Chavezazuela J, Dosaldelavega M. Placental pathology in eclampsia and preeclampsia. Obstet Gynecol 1964;24:350-6.
  73. De Wolf F, Robertson WB, Brosens I. The ultrastructure of acute atherosis in hypertensive pregnancy. Am J Obstet Gynecol 1975;123: 164-74.
  74. Staff AC, Redman CW, Williams D, et al. Pregnancy and long-term maternal cardiovas- cular health: progress through harmonization of research cohorts and biobanks. Hypertension 2016;67:251-60.
  75. Labarrere CA. Acute atherosis. A histo- pathological hallmark of immune aggression? Placenta 1988;9:95-108.
  76. Hering L, Herse F, Verlohren S, et al. Tro- phoblasts reduce the vascular smooth muscle cell proatherogenic response. Hypertension 2008;51:554-9.
  77. Herse F, Dechend R, Harsem NK, et al. Dysregulation of the circulating and tissue- based renin-angiotensin system in preeclamp- sia. Hypertension 2007;49:604-11.
  78. Rieber-Mohn AB, Sugulle M, Wallukat G, et al. Auto-antibodies against the angiotensin II type I receptor in women with uteroplacental acute atherosis and preeclampsia at delivery and several years postpartum. J Reprod Immunol 2018;128:23-9.
  79. Labarrere C, Alonso J, Manni J, Domenichini E, Althabe O. Immunohistochem- ical findings in acute atherosis associated with intrauterine growth retardation. Am J Reprod Immunol Microbiol 1985;7:149-55.
  80. Staff AC, Ranheim T, Halvorsen B. Augmented PLA2 activity in pre-eclamptic decidual tissue-a key player in the patho- physiology of 'acute atherosis' in pre- eclampsia? Placenta 2003;24:965-73.
  81. Staff AC, Ranheim T, Henriksen T, Halvorsen B. 8-iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity. Hypertension 2000;35:1307-13.
  82. Halvorsen B, Staff AC, Henriksen T, Sawamura T, Ranheim T. 8-iso-prostaglandin F(2alpha) increases expression of LOX-1 in JAR cells. Hypertension 2001;37:1184-90.
  83. Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest 2013;123:540-1.
  84. Pijnenborg R, Anthony J, Davey DA, et al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 1991;98:648-55.
  85. Kyaw T, Toh BH, Bobik A. Foxp3þCD4þ regulatory T-cell subtypes and atherosclerosis. Circ Res 2016;119:1151-3.
  86. Gill N, Leng Y, Romero R, et al. The immu- nophenotype of decidual macrophages in acute atherosis. Am J Reprod Immunol 2019;81: e13098.
  87. Moe K, Alnaes-Katjavivi P, Størvold GL, et al. Classical cardiovascular risk markers in pregnancy and associations to uteroplacental acute atherosis. Hypertension 2018;72: 695-702.
  88. Lekva T, Sugulle M, Moe K, Redman C, Dechend R, Staff AC. Multiplex analysis of circulating maternal cardiovascular biomarkers comparing preeclampsia subtypes. Hyperten- sion 2020;75:1513-22.
  89. Veerbeek JH, Brouwers L, Koster MP, et al. Spiral artery remodeling and maternal cardiovascular risk: the spiral artery remod- eling (SPAR) study. J Hypertens 2016;34: 1570-7.
  90. Stevens DU, Al-Nasiry S, Fajta MM, et al. Cardiovascular and thrombogenic risk of decidual vasculopathy in pre- eclampsia. Am J Obstet Gynecol 2014;210:545.e1-6.
  91. Sipahi I, Tuzcu EM. Candidate mechanisms for regression of coronary atherosclerosis with high-dose statins: insight from intravascular ul- trasonography trials. Am J Cardiovasc Drugs 2008;8:365-71.
  92. Lefkou E, Mamopoulos A, Dagklis T, Vosnakis C, Rousso D, Girardi G. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antith- rombotic therapy. J Clin Invest 2016;126: 2933-40. 100. Saito S, Nakashima A. A review of the mechanism for poor placentation in early- onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remod- eling. J Reprod Immunol 2014;101e102: 80-8. 101. Aoki A, Nakashima A, Kusabiraki T, et al. Trophoblast-specific conditional Atg7 knockout mice develop gestational hypertension. Am J Pathol 2018;188: 2474-86.

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Authors
Staff, A. C., Fjeldstad, H. E., Fosheim, I. K., Moe, K., Turowski, G., Johnsen, G. M., Alnaes-Katjavivi, P., & Sugulle, M.
Affiliations
Oslo University Hospital (NO)
Corresponding author
Staff, Anne Cathrine
ORCID
Venue
American Journal of Obstetrics and Gynecology
Publisher
Elsevier BV
Published
2022-02
Volume
226
Issue
2
Pages
S895-S906
ISSN
0002-9378 (ISSN-L)
DOI
10.1016/j.ajog.2020.09.026
OpenAlex
W3087168500
Cited by
354
References
2
Citations by year
2026: 67 · 2025: 65 · 2024: 75 · 2023: 61 · 2022: 54 · 2021: 32
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Obstetrics and Gynecology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
Universitetet i Oslo
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
Keywords
preeclampsia, spiral artery remodeling, acute atherosis, trophoblast invasion, decidua basalis, foam cells, maternal-fetal interface, placentation, hypertensive disorders of pregnancy
MeSH terms
Decidua, Female, Humans, Placenta, Placentation, Pre-Eclampsia, Pregnancy, Trophoblasts, Atherosclerosis, Uterine Artery, Vascular Remodeling

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