Preeclampsia: an endothelial cell disorder
Abstract
Despite intense study preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. Most investigative efforts have focused on the hypertensive component of this disorder with reduced attention given to other equally important characteristics. Increased sensitivity to pressor agents and activation of the coagulation cascade occur early in the course of preeclampsia, often antedating clinically recognizable disease. Inasmuch as endothelial cell injury reduces the synthesis of vasorelaxing agents, increases the production of vasoconstrictors, impairs synthesis of endogenous anticoagulants, and increases procoagulant production, these cells are likely to be implicated in the pathophysiology of preeclampsia. Indeed, evidence of endothelial cell injury is provided by the most characteristic morphologic lesion of preeclampsia, glomerular endotheliosis. Additional support for this hypothesis is derived from reports that indicate increased levels of circulating fibronectin (which can be released from injured endothelial cells) and increased factor VIII antigen present in the blood of preeclamptic women. More recently, direct evidence of activities that injure endothelial cells in vitro and increase the contractile sensitivity of isolated vessels has been presented. We propose that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells. The changes initiated by endothelial cell injury set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Gui et al. suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species.
“Gui et al.(75) suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species, the two mechanisms implicated in the pathophysiology of preeclampsia(84–94).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [85]
Cites
A novel potent vasoconstrictor peptide produced by vascular endothelial cells
Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y. I., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., & Masaki, T. (1988) · Nature · doi:10.1038/332411a0 · Cited by 10,716 · see citing works
Advanced Glycosylation End Products in Tissue and the Biochemical Basis of Diabetic Complications
Flier, J. S., Underhill, L. H., Brownlee, M., Cerami, A., & Vlassara, H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805193182007 · Cited by 2,512 · see citing works
Modulation of Vascular Smooth Muscle Contraction by the Endothelium
Vanhoutte, P. M., Rubanyi, G. M., Miller, V. M., et al. (1986) · Annual Review of Physiology · doi:10.1146/annurev.ph.48.030186.001515 · Cited by 650 · see citing works
Hypertensive disorders in pregnancy
Chesley, L. C. (1985) · Journal of Nurse-Midwifery · doi:10.1016/0091-2182(85)90116-8 · Cited by 632 · see citing works
Lipid peroxidation in pregnancy: New perspectives on preeclampsia
Hubel, C. A., Roberts, J. M., Taylor, R. N., Musci, T. J., Rogers, G. M., & McLaughlin, M. K. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90778-3 · Cited by 445 · see citing works
Self-citationCell biology of endothelial cells
JAFFE, E. A. (1987) · Human Pathology · doi:10.1016/s0046-8177(87)80005-9 · Cited by 368 · see citing works
Maternal Fetal Medicine. Principles and Practice
Maresh, M. (1989) · Archives of Disease in Childhood · doi:10.1136/adc.64.10.1524-b · Cited by 350 · see citing works
Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells
Rodgers, G. M., Taylor, R. N., & Roberts, J. M. (1988) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(88)80169-8 · Cited by 278 · see citing works
Self-citationHypertensive Disorders in Pregnancy
Epstein, F. H. (1978) · JAMA · doi:10.1001/jama.1978.03280470090036 · Cited by 274 · see citing works
PLASMA-URATE MEASUREMENTS IN PREDICTING FETAL DEATH IN HYPERTENSIVE PREGNANCY
Redman, C. W. G., Beilin, L. J., Bonnar, J., & Wilkinson, R. H. (1976) · The Lancet · doi:10.1016/s0140-6736(76)93024-5 · Cited by 264 · see citing works
The placental bed biopsy: Review from three European centers
Robertson, W. B., Khong, T. Y., Brosens, I. A., Wolf, F. D., SHEPPARD, B. L., & Bonnar, J. (1986) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(86)90843-4 · Cited by 225 · see citing works
Hemostatic properties of normal and perturbed vascular cells
Rodgers, G. M. (1988) · The FASEB Journal · doi:10.1096/fasebj.2.2.3277885 · Cited by 180 · see citing works
Self-citationProblems encountered in the treatment of pregnancy-induced hypertension
Zuspan, F. P. (1978) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(78)90816-5 · Cited by 132 · see citing works
Anti-vascular endothelial cell antibodies in severe preeclampsia
Rappaport, V. J., Hirata, G. I., Yap, H., et al. (1990) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(90)90836-v · Cited by 102 · see citing works
Mitogenic activity is increased in the sera of preeclamptic women before delivery
Musci, T. J., Roberts, J. M., Rodgers, G. M., & Taylor, R. N. (1988) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(88)90572-8 · Cited by 58 · see citing works
Self-citationEvans Blue Disappearance Rate in Normal and Pre-Eclamptic Pregnancy
Campbell, D. M., & Campbell, A. J. (1983) · Clinical and Experimental Hypertension Part B Hypertension in Pregnancy · doi:10.3109/10641958309023468 · Cited by 31 · see citing works
Antagonism of antihypertensive drug therapy in pregnancy by indomethacin?
Schoenfeld, A., Freedman, S., Hod, M., et al. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90666-2 · Cited by 27 · see citing works
Tulenko, T., Schneider, J., Floro, C., et al. (1987) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(87)90337-1 · Cited by 25 · see citing works
Haddy, F. J. (1980) · Clinical and Experimental Hypertension · doi:10.3109/10641968009046416 · Cited by 10 · see citing works
Anti‐vascular endothelial cell antibodies in severe preeclampsia
Rappaport, V. J., Hirata, G. I., Yap, H., et al. (1990) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(90)90681-a · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Bellamy, L., Casas, J.-P., Hingorani, A. D., & Williams, D. J. (2007) · BMJ · doi:10.1136/bmj.39335.385301.be · Cited by 2,552 · see citing works
Soluble endoglin contributes to the pathogenesis of preeclampsia
Venkatesha, S., Toporsian, M., Lam, C., Hanai, J.-I., Mammoto, T., Kim, Y. M., Bdolah, Y., Lim, K.-H., Yuan, H.-T., Libermann, T. A., et al. (2006) · Nature Medicine · doi:10.1038/nm1429 · Cited by 1,855 · see citing works
Pre-eclampsia part 1: current understanding of its pathophysiology
Chaiworapongsa, T., Chaemsaithong, P., Yeo, L., & Romero, R. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.102 · Cited by 956 · see citing works
Placental Debris, Oxidative Stress and Pre-eclampsia
Redman, C. W. G., & Sargent, I. L. (2000) · Placenta · doi:10.1053/plac.2000.0560 · Cited by 508 · see citing works
Vince, G. S., Starkey, P. M., Austgulen, R., Kwiatkowski, D., & Redman, C. W. G. (1995) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1995.tb09020.x · Cited by 381 · see citing works
Acute myocardial infarction associated with pregnancy
Roth, A., & Elkayam, U. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.03.049 · Cited by 381 · see citing works
Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology
Reiter, R. J., Tan, D. X., Korkmaz, A., & Rosales-Corral, S. A. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmt054 · Cited by 371 · see citing works
DiFederico, E., Genbacev, O., & Fisher, S. J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65123-1 · Cited by 348 · see citing works
Vascular biology of preeclampsia
Myatt, L., & Webster, R. P. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.03259.x · Cited by 292 · see citing works
Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes
Sultana, Z., Maiti, K., Aitken, J., Morris, J., Dedman, L., & Smith, R. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12653 · Cited by 288 · see citing works
Romero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H., & Grossman, L. I. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.06.003 · Cited by 253 · see citing works
Mikhail, M. S., Anyaegbunam, A., Garfinkel, D., Palan, P. R., Basu, J., & Romney, S. L. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(94)90462-6 · Cited by 229 · see citing works
Brownfoot, F. C., Hastie, R., Hannan, N. J., Cannon, P., Tuohey, L., Parry, L. J., Senadheera, S., Illanes, S. E., Kaitu’u-Lino, T. J., & Tong, S. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.12.019 · Cited by 222 · see citing works
Role of magnesium in hypertension
Sontia, B., & Touyz, R. M. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.05.005 · Cited by 202 · see citing works
If we know so much about preeclampsia, why haven’t we cured the disease?
Roberts, J. M., & Bell, M. J. (2013) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2013.05.003 · Cited by 189 · see citing works
Self-citationRecent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia
LaMarca, B. D., Gilbert, J., & Granger, J. P. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.108837 · Cited by 142 · see citing works
Abnormal iron parameters in the pregnancy syndrome preeclampsia
Rayman, M. P., Barlis, J., Evans, R. W., Redman, C. W. G., & King, L. J. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.123895 · Cited by 126 · see citing works
Bujold, E., Romero, R., Chaiworapongsa, T., KIM, Y. M., Kim, G. J., Kim, M. R., Espinoza, J., Gonçalves, L. F., Edwin, S., & Mazor, M. (2005) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050500202493 · Cited by 110 · see citing works
High-altitude hypoxia and preeclampsia
Zamudio, S. (2007) · Frontiers in Bioscience · doi:10.2741/2286 · Cited by 97 · see citing works
Szalai, G., Romero, R., Chaiworapongsa, T., Xu, Y., Wang, B., Ahn, H., Xu, Z., Chiang, P. J., Sundell, B., Wang, R., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119547 · Cited by 46 · see citing works
Holme, A. M., Roland, M. C. P., Henriksen, T., & Michelsen, T. M. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2016.07.056 · Cited by 45 · see citing works
Velzing‐Aarts, F. V., Muskiet, F. A. J., Van Der Dijs, F. P. L., & Duits, A. J. (2002) · American Journal of Reproductive Immunology · doi:10.1034/j.1600-0897.2002.01087.x · Cited by 44 · see citing works
- Authors
- Roberts, J. M., Taylor, R. N., Musci, T. J., Rodgers, G. M., Hubel, C. A., & McLaughlin, M. K.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Roberts, James M.
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 1989-11
- Volume
- 161
- Issue
- 5
- Pages
- 1200-1204
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W1983186128
- Cited by
- 1,859
- References
- 20
- Citations by year
- 2026: 19 · 2025: 16 · 2024: 27 · 2023: 40 · 2022: 38 · 2021: 46 · 2020: 34 · 2019: 41 · 2018: 47 · 2017: 47 · 2016: 46 · 2015: 48 · 2014: 65 · 2013: 62 · 2012: 67
- FWCI
- 42.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24180)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- preeclampsia, endothelial injury, endothelial dysfunction, glomerular endotheliosis, coagulation cascade, vasoconstriction, fibronectin, factor VIII, placental factors, hypertension in pregnancy, pathophysiology
- MeSH terms
- Endothelium, Vascular, Female, Humans, Models, Biological, Pre-Eclampsia, Pregnancy, Reference Values, Trophoblasts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
