Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion

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• 作者：Sol M. Bobst ; Mary-Clare Day ; Larry C. Gilstrap III ; Yang Xia ; Rodney E. Kellems
• 关键词：Preeclampsia ; angiotensin receptor ; mesangial cells ; plasminogen activator inhibitor– ; 1 ; interleukin-6 ; renal damage ; hypertension ; desseminated intravascular coagulation ; inflammation
• 刊名：American Journal of Hypertension
• 出版年：2005
• 出版时间：March 2005
• 年：2005
• 卷：18
• 期：3
• 页码：330-336
• 全文大小：241 K

文摘

Background

Preeclampsia affects 3–5 % of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT₁) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT₁ receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor–1 (Pai-1) secretion in human mesangial cells.

Methods

The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT₁ receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT₁ receptor activation.

Results

The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT₁ receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT₁ receptor was stimulated by AT1-AA.

Conclusions

Our findings suggest that a maternal autoantibody with the ability to activate AT₁ receptors may account for the development of renal damage seen in preeclamptic patients.