ABCA1, LDL receptor and STARD3 cholesterol transporter mRNA expression are upregulated in placentae from preeclamptic pregnancies

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Abstracts / Atherosclerosis xxx (2008) xxx–xxx

drate, 0.29 g protein, and 37 kJ energy per kilogram body mass) for breakfast. Venous blood samples were obtained in the fasted state (0 h), and 2, 4, and 6 h postprandially on day 2. Results: Total area under the postprandial serum triacylglycerol concentrations versus time curve was 18% (P < 0.042) and 15% (P < 0.032) lower throughout day 2 of both the accumulated exercise trial and the continuous exercise trial, respectively, compared with the control trial with little difference between exercise trials. Conclusion: Thirty minutes of moderate cycling accumulated in short bouts is equally effective in reducing postprandial serum triacylglycerol concentrations on the following day as one continuous 30 min of cycling in obese men. This study was funded by the Japan Society for the Promotion of Science and the Health Promotion Foundation, Japan. doi:10.1016/j.atherosclerosis.2008.04.023 Inhibition of cholesteryl ester transfer protein (CETP): Different in vitro characteristics of RO4607381/JTT-705 and torcetrapib (TOR) E.J. Niesor, E. von der Marck, M. Brousse, C. Maugeais F. Hoffmann-La Roche Ltd., Basel, Switzerland Aims: Biochemical relationships between CETP and RO4607381/JTT-705 or TOR in vitro were investigated. Methods: CETP inhibition IC50 values were measured in lipoprotein-deficient plasma (LPDP) and total serum, and time dependence determined using fluorescent cholesteryl ester. Effects on CETP-high-density lipoprotein (HDL) complex formation were studied with native gel electrophoresis and ultracentrifugation followed by immunoblotting. Results: CETP IC50 values for RO4607381/JTT-705 were 425 nM and 10 ␮M, and for TOR, 19 and 79 nM, in LPDP and total plasma, respectively. Time-dependent CETP inhibition was observed with RO4607381/JTT-705 (consistent with S–S bond formation with Cys13 in CETP), and not with TOR. RO4607381/JTT-705 demonstrated high specificity for CETP versus SH-containing enzymes. Gel electrophoresis showed TOR increased the binding of CETP to HDL at concentrations higher than 30 nM, consistent with the formation of an unproductive ternary complex; no similar effects were seen with RO4607381/JTT-705 up to the concentration tested of 1 ␮M. Ultracentrifugation indicated TOR at concentrations as low as 50 nM induced binding and CETP complex formation; this was not observed with RO4607381/JTT-705 up to 10 ␮M. Conclusions: Results are consistent with specific, S–S binding of RO4607381/JTT-705 to CETP without formation of a CETP-HDL complex at therapeutic plasma levels, and modulation of CETP activity via a different mechanism to TOR. doi:10.1016/j.atherosclerosis.2008.04.024

ABCA1, LDL receptor and STARD3 cholesterol transporter mRNA expression are upregulated in placentae from preeclamptic pregnancies C.C. Onyiaodike a , A. Young a , C. Lim a , A. Graham b , D.J. Freeman a a

Reproductive and Maternal Medicine, Faculty of Medicine, University of Glasgow, Glasgow, UK b Biological and Biomedical Science, Glasgow Caledonian University, Glasgow, UK Maternal hypercholesterolemia is a feature of pregnancy. Preeclampsia (PE), a hypertensive disease of pregnancy, is associated with raised maternal plasma and fetal cord total cholesterol (TC). Maternal TC correlates with atheroma area in fetal arteries. We hypothesised that in PE, cholesterol transport across the placenta is increased. Expression of cholesterol transporters was compared in term placentae from healthy (n = 20) and PE (n = 20) pregnancies (using ISSHP criteria) matched for BMI. Placental cholesterol transporters were immunolocalised. STARD protein 1–15 expression was identified using semi-quantitative PCR. Placental mRNA expression was quantitated by RT-PCR. LDLR was localised to the syncytium. ABCA1 and ABCG1 had a widespread localisation in both trophoblast and fetal endothelial cells. STARD cholesterol transporters 1, 3, 4 and 5 were found to be expressed by placenta. ABCA1, ABCG1and LDLR were quantitated relative to 18 s. ABCA1 [mean (S.E.); 360 (67) PE vs. 108 (21) control target/18s ratio × 10−4 , P = 0.001], LDLR [424 (125) vs. 140 (28), P = 0.039] and STARD3 [734 (107) vs. 446 (75), P = 0.035] mRNA expression was higher in PE. ABCA1 mRNA correlated with maternal TC in the total (r = 0.45, P = 0.004) and PE (r = 0.63, P = 0.003) groups. In conclusion, localisation of LDLR and ABCA1 at the maternal/fetal interface is consistent with a role in placental cholesterol transport. Higher placental LDLR, ABCA1 and STARD3 mRNA expression in PE may lead to increased cholesterol delivery to the fetus. doi:10.1016/j.atherosclerosis.2008.04.025 Hyperglycaemic patients have decreased ATP-binding cassette transporter-A1 (ABCA-1) gene expression: A novel disease mechanism D.C. Patel a , D. Pavitt a , C. Albrecht b , S. Dhanjil e , R. Hannen c , J. Valabhji a , C.F. Higgins d , D.G. Johnston a a

Metabolic Medicine, Imperial College, London, UK of Bern, London, UK c Institute of Cell and Molecular Science, London, UK d Clinical Sciences Centre, Imperial College, UK e Irvine Vascular Studies, St. Mary’s Hospital, UK b University

Type 2 diabetes (DM) and impaired glucose tolerance (IGT) are common conditions associated with premature coronary heart disease (CHD). Epidemiological studies indi-

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