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Journal of Lipid Research, Vol. 50, 1967-1975, October 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Proteomics

Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins

Andrew N. Hoofnagle^1,* and Jay W. Heinecke

^* Department of Laboratory Medicine, University of Washington, Seattle, WA
Department of Medicine, University of Washington, Seattle, WA

¹ To whom correspondence should be addressed. e-mail: ahoof{at}u.washington.edu

Lipoproteins are centrally important in lipid transport, fuel metabolism, and cardiovascular disease. The prototypic lipoprotein has an outer shell of amphipathic lipids and proteins that solubilizes a hydrophobic lipid core. Lipoprotein-associated proteins have classically been viewed as structural elements and factors important in lipid metabolism. Recent mass spectrometric analyses reveal that the protein cargo of lipoproteins is much more diverse than previously appreciated, raising the possibility that lipoproteins play previously unsuspected roles in host defense mechanisms and inflammation. They further suggest that lipoprotein-associated proteins can identify humans at increased risk of cardiovascular disease. Here, we summarize recent developments in lipoproteomics, the proteomic analysis of lipoproteins. We also discuss the promises and challenges this powerful analytical strategy offers for expanding our understanding of the biology and structures of lipoproteins.

Supplementary key words cardiovascular disease • lipoprotein metabolism • innate immunity • inflammation • macrophages

Abbreviations: apo, apolipoprotein; CVD, cardiovascular disease; CETP, cholesteryl ester transfer protein; GO, Gene Ontology; LC-ESI-MS/MS, liquid chromatography-electrospray ionization-tandem mass spectrometry; MALDI-TOF-MS, matrix assisted laser desorption ionization-time of flight-MS; PLTP, phospholipid transfer protein; PON, paraoxonase; 2D, two-dimensional

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