Overexpression of Apolipoprotein F Reduces HDL Cholesterol Levels In Vivo

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 29; no. 1; pp. 40 - 46
• Main Authors: Lagor, William R., Brown, Robert J., Toh, Sue-Anne, Millar, John S., Fuki, Ilia V., de la Llera-Moya, Margarita, Yuen, Tiffany, Rothblat, George, Billheimer, Jeffrey T., Rader, Daniel J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-01-2009; Lippincott Williams & Wilkins
• Subjects: Alanine Transaminase - blood; Animals; Apolipoproteins - blood; Apolipoproteins - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Bone Marrow - physiology; Cardiology. Vascular system; Cell Line; Cholesterol - blood; Cholesterol - metabolism; Cholesterol, HDL - blood; Cloning, Molecular; Coronary heart disease; Dependovirus - genetics; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Gene Expression Regulation; Heart; Humans; Kidney - embryology; Macrophages - physiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Phospholipids - blood; Plasmids; Triglycerides - blood; reverse cholesterol transport; Cardiovascular disease; adeno-associated virus; Apolipoprotein; HDL cholesterol; Vascular disease; Virus; Associated virus; Cholesterol HDL; Atherosclerosis; apolipoprotein F; lipid transfer inhibitor protein; Transport
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.108.177105

Apolipoprotein F (ApoF) is a protein component of several lipoprotein classes including HDL. It is also known as lipid transfer inhibitor protein (LTIP) based on its ability to inhibit lipid transfer between lipoproteins ex vivo. We sought to investigate the role of ApoF in HDL metabolism.
Adeno-associated viruses (AAV) based on serotype 8, were used to overexpress either murine or human ApoF in mice. Overexpression of murine ApoF significantly reduced total cholesterol levels by 28% (P<0.001), HDL by 27% (P<0.001), and phospholipid levels by 19% (P<0.001). Overexpression of human ApoF had similar effects. Human ApoF was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the ApoF in human plasma was found on HDL(3), with only a small amount on LDL. Overexpression of mouse ApoF accelerated the plasma clearance of [(3)H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing ApoF showed improved macrophage cholesterol efflux on a per HDL-C basis.
ApoF overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. ApoF may be an important determinant of HDL metabolism and reverse cholesterol transport.