Lamellar lipoproteins uniquely contribute to hyperlipidemia in mice doublydeficient in apolipoprotein E and hepatic lipase

Remnants of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 accumulate in apo E-deficient mice, causing pronounced hypercholestero lemia. Mice doubly deficient in apo E and hepatic lipase have more pronounc ed hypercholesterolemia, even though remnants do not accumulate appreciably in mice deficient in hepatic lipase alone. Here we show that the doubly de ficient mice manifest a unique lamellar hyperlipoproteinemia, characterized by vesicular particles 600 Angstrom-1,300 Angstrom 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 ves icle wall is composed of a 1:1 molar mixture of cholesterol and phospholipi ds, whereas the electron-lucent region appears to be composed of cholestery l esters (about 12% of the particle mass), Like the spherical lipoproteins of doubly deficient mice, the vesicular particles contain apo B-48, but the y 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 lip oproteins. Hepatic lipase may prevent such vesicular lipoproteins from accu mulating in apo E-deficient mice by hydrolyzing phosphatidyl choline as sca venger receptor B1 removes the cholesteryl esters and by gradual endocytosi s of lipoproteins bound to hepatic lipase on the surface of hepatocytes.