Transendothelial lipoprotein transport and regulation of endothelial permeability and integrity by lipoproteins.
OBJECTIVE
Previously, the endothelium was considered as a passive exchange barrier of lipoproteins between plasma and extravascular tissues. This dogma is challenged by recent findings on a dual relationship between lipoproteins and endothelial permeability.


RESULTS
LDL and HDL as well as apolipoprotein A-I pass the intact endothelium through transcytosis by processes, which involve caveolin-1, the LDL-receptor, ATP-binding cassette transporters A1 and G1 or scavenger receptor BI. Moreover, HDL help the endothelium to maintain structural integrity and hence selective permeability for biomolecules by keeping interendothelial junctions closed, by inhibiting endothelial cell apoptosis and by stimulating endothelial proliferation, migration and tube formation as well as the recruitment and differentiation of endothelial progenitor cells in damaged parts of the endothelium. Both apolipoprotein A-I and sphingosin-1-phosphate mediate many of the protective effects of HDL on the endothelium by interacting with endothelial scavenger receptor BI and sphingosin-1-phosphate receptors, respectively, and by activating intracellular signalling cascades, including the small G protein Rac, src-kinase, phosphoinositol 3 kinase, protein kinase B (Akt) and mitogen-activated protein kinases.


CONCLUSIONS
The endothelium actively controls the trafficking of lipoproteins between intravascular and extravascular compartments. In addition, lipoproteins affect the integrity and permeability of the endothelium.
von Eckardstein
Arnold
A
Institute of Clinical Chemistry and Zurich Centre for Integrative Human Physiology, University Hospital and University of Zurich, Zurich, Switzerland. arnold.voneckardstein@usz.ch
Rohrer
Lucia
L
D000818:Animals; D002470:Cell Survival; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D010539:Permeability; D021381:Protein Transport
D008074:Lipoproteins