PAPP-A negatively regulates ABCA1, ABCG1 and SR-B1 expression by inhibiting LXRα through the IGF-I-mediated signaling pathway

• Published in: Atherosclerosis 2012-06, Vol.222 (2), p.344-354
• Main Authors: Tang, Shi-Lin, Chen, Wu-Jun, Yin, Kai, Zhao, Guo-Jun, Mo, Zhong-Cheng, Lv, Yun-Cheng, Ouyang, Xin-Ping, Yu, Xiao-Hua, Kuang, Huai-Jun, Jiang, Zhi-Sheng, Fu, Yu-Chang, Tang, Chao-Ke
• Format: Article
• Language: English
• Subjects: ABCA1; ABCG1; agonists; Arterial hypertension. Arterial hypotension; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - etiology; Atherosclerosis - genetics; Atherosclerosis - metabolism; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cell Line; cholesterol; Cholesterol - metabolism; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Down-Regulation; foam cells; Foam Cells - drug effects; Foam Cells - metabolism; Gene Expression Regulation; Humans; IGF-1/PI3-K/Akt signaling pathway; insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Liver X Receptors; LXRα; Medical sciences; messenger RNA; mitogen-activated protein kinase; nitric oxide; Orphan Nuclear Receptors - metabolism; PAPP-A; pathogenesis; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - metabolism; Pregnancy-Associated Plasma Protein-A - metabolism; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; RNA Interference; RNA, Messenger - metabolism; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Signal Transduction; small interfering RNA; SR-BI; Time Factors; transcription (genetics); Transcription, Genetic; Transfection
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.03.005

Highlights ► In the present study, we first found that PAPP-A inhibits ABCA1, ABCG1, SR-BI expression and reduces cholesterol efflux in THP-1 macrophage-derived foam cells. ► LXRα is involved in PAPP-A-induced down-regulation of ABCA1, ABCG1 and SR-BI in cells. ► PAPP-A promotes the IGF-1/PI3-K/Akt signaling pathway in cells. ► The IGF-1/PI3-K/Akt signaling pathway may be related to down-regulated expression of LXRα, ABCA1, ABCG1 and SR-BI by PAPP-A in THP-1 macrophage-derived foam cells.