Elevated plasma endothelial microparticles: Preeclampsia versus gestational hypertension

doi:10.1016/j.ajog.2004.06.044

American Journal of Obstetrics and Gynecology

Volume 191, Issue 4, October 2004, Pages 1418-1424

https://doi.org/10.1016/j.ajog.2004.06.044 Get rights and content

Objective

Elevated plasma endothelial microparticle levels have been found to be elevated in women with preeclampsia. However, their role in distinguishing preeclampsia from gestational hypertension remains to be elucidated. The objectives of this study were to compare endothelial microparticle levels among patients with preeclampsia, gestational hypertension, and healthy pregnant control subjects and to evaluate the effect of plasma from women with preeclampsia and gestational hypertension on the release of endothelial microparticles by renal microvascular endothelial cells.

Study design

A prospective study was conducted on 52 women with preeclampsia, 20 women with gestational hypertension, and 38 healthy pregnant control subjects. Endothelial microparticles were measured by flow cytometry with fluorescent monoclonal mouse anti-human antibodies against CD31, CD42b, and CD62E.

Results

CD31⁺/42b⁻ endothelial microparticle levels were 10497 ± 5145 counts/μL in women with preeclampsia versus 6768 ± 1810 counts/μL in women with gestational hypertension (P < .01). In control subjects, CD31⁺/42b⁻ endothelial microparticle levels were 6119 ± 3592 counts/μL. CD62E⁺ endothelial microparticle levels were1930 ± 966 counts/μL in women with preeclampsia versus 822 ± 150 counts/μL in women with gestational hypertension (P <.01). In control subjects, CD62E⁺ endothelial microparticle levels were 712 ± 160 counts/μL. Incubation of renal microvascular endothelial cells with plasma from women with preeclampsia resulted in a rise in CD31⁺ and CD62E⁺ endothelial microparticle levels as compared with women with gestational hypertension and control subjects.

Conclusion

Endothelial microparticle levels are higher in women with preeclampsia than in women with gestational hypertension and control subjects. The measurement of endothelial microparticles may be useful as a diagnostic tool for preeclampsia in pregnant women.

Section snippets

Patient and control population

This prospective, case-control study was conducted with 52 women with preeclampsia, 20 women with gestational hypertension, and 38 healthy pregnant women who were recruited from our university hospital from July 2002 to February 2003. Approval from the University of Miami Institutional Review Board was obtained, and each woman provided informed consent before enrollment. The Working Group Report on High Blood Pressure in Pregnancy defined the criteria that were used for the selection of study

Results

No significant difference was noted between study and control women with respect to age or gravity. However, there were statistical differences in the gestational age at study enrollment between the patients with preeclampsia and gestational hypertension relative to the control subjects. There were 9 cases of severe preeclampsia that met inclusion criteria. As anticipated by the diagnostic criteria that were used for recruitment of study participants, the MAP pressures were elevated

Comment

The true cause of preeclampsia continues to be debated. In recent years, the theory of endothelial dysfunction has been gaining momentum, with the identification of circulating soluble endothelial adhesion molecules (such as VCAM-1, ICAM-1, CD31, E-selectin, and fibronectin) in the plasma of women with preeclampsia.16., 17., 18., 19., 20., 21. These adhesion molecules are expressed constitutively on the endothelial cell surface and are cytokine-inducible, which is known to regulate the

References (25)

J.R. Barton et al.
Mild gestational hypertension remote for term: progression and outcome
Am J Obstet Gynecol
(2001)
J.M. Roberts et al.
Preeclampsia: more than pregnancy-induced hypertension
Lancet
(1993)
V.H. Gonzalez-Quintero et al.
Elevated plasma endothelial microparticles in preeclampsia
Am J Obstet Gynecol
(2003)
R. Austgulen et al.
Increased maternal plasma levels of soluble adhesion molecules (ICAM-1, V-CAM-1, E-selectin) in preeclampsia
Eur J Obstet Gynecol Reprod Biol
(1997)
T. Clausen et al.
Altered circulating levels of adhesion molecules at 18 weeks' gestation among women with eventual preeclampsia: Indicators of disturbed placentation in absence of evidence of endothelial dysfunction?
Am J Obstet Gynecol
(2000)
W. Heyl et al.
The role of soluble adhesion molecules in evaluating endothelial cell activation in preeclampsia
Am J Obstet Gynecol
(1999)
W. Heyl et al.
Elevated soluble adhesion molecules in women with pre-eclampsia: Do cytokines like tumour necrosis factor-α and interleukin-1β cause endothelial activation?
Eur J Obstet Gynecol Reprod Biol
(1999)
A.K. Smarason et al.
Endothelial cell proliferation is suppressed by plasma but not serum from women with preeclampsia
Am J Obstet Gynecol
(1996)
M.J. Kupferminc et al.
Tumor necrosis factor-α is elevated in plasma and amniotic fluid of patients with severe preeclampsia
Am J Obstet Gynecol
(1994)
Report of the National High Blood Pressure Education Program Working Group: report on high blood pressure in pregnancy
Am J Obstet Gynecol
(2002)

P. Saudan et al.

Does gestational hypertension become preeclampsia?

BJOG

(1998)

J. Roberts

Endothelial dysfunction in preeclampsia

Semin Reprod Endocrinol

(1998)

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Citation Excerpt :
This suggests that there are common pathophysiologies between the two diseases involving a pro-inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism. One study looking at EMPs found that not only are levels higher in hypertensive patients compared to normotensive patients but that they are also higher in women with PE compared to women with gestational hypertension [9]. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase and thus less nitric oxide.
Left ventricular diastolic dysfunction, the main feature of heart failure with preserved ejection fraction (HFpEF), is thought to be primarily caused by comorbidities affecting the endothelial function of the coronary microvasculature. Circulating extracellular vesicles, released by the endothelium have been postulated to reflect endothelial damage. Therefore, we reviewed the role of extracellular vesicles, in particularly endothelium microparticles, in these comorbidities, including obesity and hypertension, to identify if they may be potential markers of the endothelial dysfunction underlying left ventricular diastolic dysfunction and HFpEF.

View all citing articles on Scopus

: Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal Medicine, February 2-7, 2004, New Orleans, La.

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Transactions of the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal MedicineElevated plasma endothelial microparticles: Preeclampsia versus gestational hypertension

Objective

Study design

Results

Conclusion

Section snippets

Patient and control population

Results

Comment

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Am J Obstet Gynecol

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Am J Obstet Gynecol

Am J Obstet Gynecol

Report of the National High Blood Pressure Education Program Working Group: report on high blood pressure in pregnancy

Am J Obstet Gynecol

Does gestational hypertension become preeclampsia?

BJOG

Endothelial dysfunction in preeclampsia

Semin Reprod Endocrinol

Transactions of the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal Medicine
Elevated plasma endothelial microparticles: Preeclampsia versus gestational hypertension