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Int J Biol Sci 2009; 5(5):489-499. doi:10.7150/ijbs.5.489 This issue Cite

Research Paper

An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration

Xun Chen, Charlotte Burton, Xuelei Song, Lesley Mcnamara, Annunziata Langella, Simona Cianetti, Ching H. Chang, Jun Wang✉

Merck Research Laboratories, Rahway, New Jersey 07065, USA

✉ Correspondence to: Jun Wang, Ph.D., Department of Biology, Sundia MediTech Company, Ltd. Building 8, 388 Jialilue Road, Zhangjiang Hightech Park, Shanghai 201203, China Tel: 86-21-51098642 x 128; Fax: 86-21-51903505 E-mail: jwangcom

Citation:
Chen X, Burton C, Song X, Mcnamara L, Langella A, Cianetti S, Chang CH, Wang J. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. Int J Biol Sci 2009; 5(5):489-499. doi:10.7150/ijbs.5.489. https://www.ijbs.com/v05p0489.htm
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Abstract

Lecithin cholesterol acyltransferase (LCAT) plays a key role in the reverse cholesterol transport (RCT) process by converting cholesterol to cholesteryl ester to form mature HDL particles, which in turn deliver cholesterol back to the liver for excretion and catabolism. HDL levels in human plasma are negatively correlated with cardiovascular risk and HDL functions are believed to be more important in atheroprotection. This study investigates whether and how D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, influences LCAT activity in the completion of the RCT process. We demonstrated that the apparent rate constant value of the LCAT enzyme reaction gives a measure of LCAT activity and determined the effects of free metals and a reducing agent on LCAT activity, showing an inhibition hierarchy of Zn2+>Mg2+>Ca2+ and no inhibition with β-mercaptoethanol up to 10 mM. We reconstituted nano-disc particles using apoA-I or D-4F with phospholipids. These particles elicited good activity in vitro in the stimulation of cholesterol efflux from macrophages through the ATP-binding cassette transporter A1 (ABCA1). With these particles we studied the LCAT activity and demonstrated that D-4F did not activate LCAT in vitro. Furthermore, we have done in vivo experiments with apoE-null mice and demonstrated that D-4F (20 mg/kg body weight, once daily subcutaneously) increased LCAT activity and HDL level as well as apoA-I concentration at 72 hours post initial dosing. Finally, we have established a correlation between HDL concentration and LCAT activity in the D-4F treated mice.

Keywords: D-4F, lipoprotein, apoE, HDL, RCT, atherosclerosis, LCAT

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APA
Chen, X., Burton, C., Song, X., Mcnamara, L., Langella, A., Cianetti, S., Chang, C.H., Wang, J. (2009). An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. International Journal of Biological Sciences, 5(5), 489-499. https://doi.org/10.7150/ijbs.5.489.

ACS
Chen, X.; Burton, C.; Song, X.; Mcnamara, L.; Langella, A.; Cianetti, S.; Chang, C.H.; Wang, J. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. Int. J. Biol. Sci. 2009, 5 (5), 489-499. DOI: 10.7150/ijbs.5.489.

NLM
Chen X, Burton C, Song X, Mcnamara L, Langella A, Cianetti S, Chang CH, Wang J. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. Int J Biol Sci 2009; 5(5):489-499. doi:10.7150/ijbs.5.489. https://www.ijbs.com/v05p0489.htm

CSE
Chen X, Burton C, Song X, Mcnamara L, Langella A, Cianetti S, Chang CH, Wang J. 2009. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. Int J Biol Sci. 5(5):489-499.

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