Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.
Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.
Yagyu
H
H
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Ishibashi
S
S
Chen
Z
Z
Osuga
J
J
Okazaki
M
M
Perrey
S
S
Kitamine
T
T
Shimada
M
M
Ohashi
K
K
Harada
K
K
Shionoiri
F
F
Yahagi
N
N
Gotoda
T
T
Yazaki
Y
Y
Yamada
N
N
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002788:Cholesterol Esters / Q000096:biosynthesis; D004036:Diet, Atherogenic; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins; D008071:Lipoprotein Lipase