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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arterioscler Thromb Vasc Biol. Author manuscript; available in PMC Jan 1, 2010.
Published in final edited form as:
PMCID: PMC2766561

Overexpression of Apolipoprotein F reduces HDL cholesterol levels in vivo


Apolipoprotein F (Apo F) 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 Apo F in HDL metabolism.

Methods and Results

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 Apo F had similar effects. Human Apo F was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the Apo F in human plasma was found on HDL3, with only a small amount on LDL. Overexpression of mouse Apo F accelerated the plasma clearance of [3H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing Apo F showed improved macrophage cholesterol efflux on a per HDL-C basis.


Apo F overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. Apo F may be an important determinant of HDL metabolism and reverse cholesterol transport.

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