Placental ABCA1 expression is reduced in primary antiphospholipid syndrome compared to pre-eclampsia and controls.
The ATP binding cassette transporter A1 (ABCA1) mediates cellular cholesterol and phospholipid efflux, and is implicated in phosphatidylserine translocation and apoptosis. Loss of functional ABCA1 in null mice results in severe placental malformation. This study aimed to establish the placental localisation of ABCA1 and to investigate whether ABCA1 expression is altered in placentas from pregnancies complicated by pre-eclampsia and antiphospholipid syndrome. ABCA1 mRNA and protein localisation studies were carried out using in situ hybridization and immunohistochemistry. Comparisons of gene expression were performed using real-time PCR and immunoblotting. ABCA1 mRNA and protein was localised to the apical syncytium of placental villi and endothelia of fetal blood vessels within the villi. ABCA1 mRNA expression was reduced in placentas from women with APS when compared to controls (p<0.001), and this was paralleled by reductions in ABCA1 protein expression. There were no differences in ABCA1 expression between placentas from pre-eclamptic pregnancies and controls. The localisation of ABCA1 in human placenta is consistent with a role in cholesterol and phospholipid transport. The decrease in ABCA1 protein in APS may reflect reduced cholesterol transport to the fetus affecting the formation of cell membranes and decreasing the level of substrate available for steroidogenesis.
Albrecht
C
C
MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Soumian
S
S
Tetlow
N
N
Patel
P
P
Sullivan
M H F
MH
Lakasing
L
L
Nicolaides
K
K
Williamson
C
C
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger