Premium
Effects of Highly Active Antiretroviral Therapy on Reverse Cholesterol Transport
Author(s) -
Lee YunKyung,
Nerurkar Vivek R,
Frank Jennifer E,
Nerurkar Pratibha V
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a487
Subject(s) - cholesterol 7 alpha hydroxylase , abca1 , reverse cholesterol transport , cholesterol , farnesoid x receptor , liver x receptor , reverse transcriptase inhibitor , dyslipidemia , pharmacology , bile acid , nuclear receptor , biology , chemistry , transporter , lipoprotein , medicine , biochemistry , virology , antiretroviral therapy , human immunodeficiency virus (hiv) , gene , viral load , disease , transcription factor
Long‐term usage of protease inhibitor (PI)‐containing regimens to treat HIV infection, has been associated with adverse events including dyslipidemia. PI can significantly increase serum triglycerides, cholesterol and decrease high density lipoprotein (HDL)‐cholesterol among seronegativeand HIV‐infected patients. Our aim was to investigate effects of combination of antiretroviral drugs on reverse cholesterol transport using human hepatoma cell line, HepG2 and C57BL/6 mouse model systems. Our in vitro data indicates that PI significantly inhibited mRNA expression of cytochrome P450 7A1 (CYP7A1), that catalyzes the first rate‐limiting step in the conversion of cholesterol to bile acids. PI also inhibited the ATP‐binding cassette transporter (ABCA1) gene expression that transports intracellular cholesterol and phospholipids to cell surface‐bound apolipoproteins and forms nascent HDL. Both, CYP7A1 and ABCA1 are negatively regulated by the nuclear receptor, farensoid X‐receptor (FXR). In our studies PI significantly increased expression of FXR and liver X receptor (LXR) in HepG2 cells (p<0.05). We are currently investigating molecular mechanisms of reverse cholesterol transport in C57BL/6 mice treated with and without combination of antiretroviral drugs. Understanding the molecular mechanisms can help to identify new molecular targets to treat HAART‐associated metabolic disorders. [Partially supported by a grant (G12RR003061) from the RCMI Program NCRR, NIH]