Lamellar lipoproteins uniquely contribute to hyperlipidemia in mice doubly deficient in apolipoprotein E and hepatic lipase.
Remnants of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 accumulate in apo E-deficient mice, causing pronounced hypercholesterolemia. Mice doubly deficient in apo E and hepatic lipase have more pronounced hypercholesterolemia, even though remnants do not accumulate appreciably in mice deficient in hepatic lipase alone. Here we show that the doubly deficient mice manifest a unique lamellar hyperlipoproteinemia, characterized by vesicular particles 600 A-1,300 A in diameter. As seen by negative-staining electron microscopy, these lipoproteins also contain an electron-lucent region adjacent to the vesicle wall, similar to the core of typical lipoproteins. Correlative chemical analysis indicates that the vesicle wall is composed of a 1:1 molar mixture of cholesterol and phospholipids, whereas the electron-lucent region appears to be composed of cholesteryl esters (about 12% of the particle mass). Like the spherical lipoproteins of doubly deficient mice, the vesicular particles contain apo B-48, but they are particularly rich in apo A-IV. We propose that cholesteryl esters are removed from spherical lipoproteins of these mice by scavenger receptor B1, leaving behind polar lipid-rich particles that fuse to form vesicular lipoproteins. Hepatic lipase may prevent such vesicular lipoproteins from accumulating in apo E-deficient mice by hydrolyzing phosphatidyl choline as scavenger receptor B1 removes the cholesteryl esters and by gradual endocytosis of lipoproteins bound to hepatic lipase on the surface of hepatocytes.
Bergeron
N
N
Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, CA 94143, USA.
Kotite
L
L
Verges
M
M
Blanche
P
P
Hamilton
R L
RL
Krauss
R M
RM
Bensadoun
A
A
Havel
R J
RJ
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D006937:Hypercholesterolemia / Q000097:blood* / Q000235:genetics; D008049:Lipase / Q000172:deficiency* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010743:Phospholipids / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008074:Lipoproteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase