Figure 7
ABCA1 and ABCG1 are upregulated in whole blood from human subjects following single-dose LXR-623. Panels A and B. Ten-fold dilutions (ranging from 10 to 100,000,000 copies) of ABCA1 and ABCG1 in vitro transcripts were reverse transcribed into cDNA and PCR amplified on an ABI 7900 real time PCR system. Representative amplification plots are shown for ABCA1 (A) and ABCG1 (B) with each dilution analyzed in triplicate (the 10 copy dilution standards gave CT's > 40 and are not shown on the graphs). For each analytical run, standard curves were generated from a dilution series of the calibrator transcripts to allow accurate copy number estimation in clinical RNA samples. Panels C and D: whole blood was collected into PAXgene tubes two hours prior to dosing (-2 h) and at 2 h, 4 h, 12 h, 24 h and 48 h following a single dose of LXR-623. Time course results for a single representative subject receiving 75 mg/kg LXR-623 are depicted for both ABCA1 (C) and ABCG1 (D) transcript levels. ABCA1 and ABCG1 transcript levels are expressed as actual copy numbers per million copies of GAPDH. Both transcripts exhibited similar fold elevations and followed identical time courses after LXR-623 exposure, with a maximal induction by 4 hours followed by a return to baseline levels after 24 hours.