Professional Documents
Culture Documents
115]121
Article
Abstract
Objecti e: To evaluate the levels of VCAM-1 in pre-eclampsiareclampsia as a possible marker of leukocyte
activation and endothelial damage. Methods: We performed a case-control study on 25 healthy pregnant women and
35 patients diagnosed as pre-eclampsia or eclampsia which were randomly selected. Peripheral venous blood samples
were obtained and serum levels of VCAM-1 were measured by enzyme-linked immunoassay ELISA.. Results: In
pre-eclampsiareclampsia, VCAM-1 levels were higher than in normal pregnancy. Serum concentrations of VCAM-1
were significantly higher in severe pre-eclampsia and eclampsia compared to mild pre-eclampsia or healthy controls.
ROC analysis detected that VCAM-1 G 450 ngrml had a sensitivity of 0.79 and a specificity of 0.90 in detecting
severe pre-eclampsia and eclampsia. Conclusion: This is the first study to correlate VCAM-1 levels with severity of
disease in pre-eclampsia. Our findings indicate that increasing levels of soluble VCAM-1 are present in the
circulation of patients with severe pre-eclampsiareclampsia compared to mild pre-eclampsia or healthy pregnant
women. Elevated VCAM-1 levels may represent a possible mechanism by which endothelial cells attract leukocytes
and cause endothelial cell damage. Q 1998 International Federation of Gynecology and Obstetrics
Keywords: Vascular cell adhesion molecule-1; Endothelial damage; Pre-eclampsia
Corresponding author. Tel.: q90 212 5861514; fax: q90 212 586 1514; e-mail: ebudak@hotmail.com
0020-7292r98r$ - see front matter Q 1998 International Federation of Gynecology and Obstetrics
PII S0020-729298.00138-6
116
1. Introduction
Increasing evidence suggests that generalized
endothelial cell damage and dysfunction are major pathophysiologic features of pre-eclampsia
w1]3x. Although, the mechanisms of endothelial
activation and dysfunction are yet unclear, there
is substantial evidence suggesting that leukocyteinstigated damage contribute to this process w4]6x.
Recently, studies have attempted to identify
markers of leukocyte activation and leukocyte
initiated endothelial damage in pre-eclampsia
w7]9x.
VCAM-1 is a cell adhesion molecule and a
member of the immunoglobulin supergene family
w10x. VCAM-1 has a single chain glycoprotein
structure and functions as a transmembrane receptor in vascular endothelial cell membranes.
Very late antigen-4 VLA-4., a a 4 b 1 integrin, is
the counter ligand of VCAM-1 and is expressed
by neutrophils, monocytes, lymphocytes, basophils, eosinophils and certain tumor cells w11,12x.
Cytokines and other pro-inflammatory substances
stimulate the production of endothelial cell adhesion molecules and their transport to the cell
membrane w13,14x. Concurrently, after induction
by chemostimulants or specific signals, leukocytes
become activated and adhere to endothelial cells,
by binding to VCAM-1 w15x. Leukocytes become
firmly attached to vascular endothelium and
rapidly migrate into tissues through gaps within
the endothelial lining to take part in inflammatory processes. When the primary insult is exerted
for a prolonged duration, as in chronic inflammation or autoimmune disorders, leukocyte activation and recruitment to the involved area may
accentuate the initial insult and ultimately may
become a primary cause of tissue injury w4x.
It is believed that VCAM-1 can be utilized as a
marker to monitor endothelial and leukocyte activation w9,16]18x. VCAM-1 levels have been demonstrated to correlate with disease state progression w19]22x. The purpose of the present study
was to measure circulating VCAM-1 levels in
normal pregnant women and pre-eclampsia, and
to determine if disease severity in pre-eclampsia
is correlated with serum VCAM-1 concentrations.
117
Fig. 1. Scattergram display of distribution of VCAM-1 concentrations in relation to disease severity in pre-eclampsia. Individual
VCAM-1 levels are shown for 25 healthy pregnant women, 16 mild pre-eclampsia, 16 severe pre-eclampsia and three eclampsia
patients.
118
Fig. 2. VCAM-1 levels of patients in the hypertensive group in relation to diastolic blood pressure elevation.
4. Discussion
119
Fig. 3. Receiver-operating characteristic curves of sensitivity and specificity of severe pre-eclampsia plus eclampsia s severe disease
curve 1., mild and severe pre-eclampsia plus eclampsia curve 2. and mild pre-eclampsia curve 3. in relation to the reference curve
curve 4.. The ROC curve for severe disease is clearly superior to other curves. This difference is particularly apparent in the area
of high specificity, where the curve is higher and more to the left than that of the other curves.
120
w9x
w10x
w11x
w12x
w13x
w14x
w15x
w16x
w17x
Johnston TA. Immunocytochemical localization of neutrophil elastase in term placenta decidua and myometrium in pregnancy-induced hypertension. Br J
Obstet Gynaecol 1991;98:929]933.
Lyall F, Greer IA, Boswell F, Macara LM, Walker JJ,
Kingdom JC. The cell adhesion molecule, VCAM-1, is
selectively elevated in serum in pre-eclampsia: does this
indicate the mechanism of leucocyte activation? Br J
Obstet Gynaecol 1994;101:485]487.
Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj
S, Chi-Rosso G et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell
1989;59:1203]1211.
Frenette PS, Wagner DD. Adhesion molecules-Part 1. N
Engl J Med 1996;334:1526]1529.
Reinhardt PH, Elliott JF, Kubes P. Neutrophils can
adhere via alpha4beta1-integrin under flow conditions.
Blood 1997;89:3837]3846.
Iademarco MF, Barks JL, Dean DC. Regulation of
vascular cell adhesion molecule-1 expression by IL-4
and TNF-alpha in cultured endothelial cells. J Clin
Invest 1995;95:264]271.
Greer IA, Lyall F, Perera T, Boswell F, Macara LM.
Increased concentrations of cytokines interleukin-6 and
interleukin-1 receptor antagonist in plasma of women
with pre-eclampsia: a mechanism for endothelial dysfunction? Obstet Gynecol 1994;84:937]940.
Adams DH, Lloyd AR. Chemokines: leucocyte recruitment and activation cytokines. Lancet 1997;349:490]495.
Gearing AJH, Newman W. Circulating adhesion
molecules in disease. Immunol Today 1993;14:506]512.
Haller H, Ziegler EM, Homuth V et al. Endothelial
adhesion molecules and leukocyte integrins in preeclamptic patients. Hypertension 1997;29:291]296.
121