Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins
Article first published online: 1 NOV 2012
© 2012 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 272, Issue 6, pages 528–540, December 2012
How to Cite
Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins (Review). J Intern Med 2012; doi: 10.1111/joim.12003., , , , , (David Geffen School of Medicine, University of California, Los Angeles, CA; Cornell University, Ithaca, NY, USA).
- Issue published online: 20 NOV 2012
- Article first published online: 1 NOV 2012
- Accepted manuscript online: 1 OCT 2012 01:14AM EST
- National Institutes of Health. Grant Numbers: R01 HL094732, P01 HL090553, R01 HL087228
- endothelial cells;
- glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1;
- lipoprotein lipase;
- lymphocyte antigen 6 proteins
Lipoprotein lipase (LPL) is produced by parenchymal cells, mainly adipocytes and myocytes, but is involved in hydrolysing triglycerides in plasma lipoproteins at the capillary lumen. For decades, the mechanism by which LPL reaches its site of action in capillaries was unclear, but this mystery was recently solved. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells, ‘picks up’ LPL from the interstitial spaces and shuttles it across endothelial cells to the capillary lumen. When GPIHBP1 is absent, LPL is mislocalized to the interstitial spaces, leading to severe hypertriglyceridaemia. Some cases of hypertriglyceridaemia in humans are caused by GPIHBP1 mutations that interfere with the ability of GPIHBP1 to bind to LPL, and some are caused by LPL mutations that impair the ability of LPL to bind to GPIHBP1. Here, we review recent progress in understanding the role of GPIHBP1 in health and disease and discuss some of the remaining unresolved issues regarding the processing of triglyceride-rich lipoproteins.