Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia.
BACKGROUND
Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease.


OBJECTIVE
Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology.


METHODS
AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA.


METHODS
Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed.


RESULTS
Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15).


CONCLUSIONS
We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.
Stepan
H
H
Department of Cardiology and Pneumonology, Charité-Universitätsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Faber
R
R
Wessel
N
N
Wallukat
G
G
Schultheiss
H-P
HP
Walther
T
T
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D012189:Retrospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1