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Publication : Effects of heterozygous lipoprotein lipase deficiency on diet-induced atherosclerosis in mice.

First Author  Semenkovich CF Year  1998
Journal  J Lipid Res Volume  39
Issue  6 Pages  1141-51
PubMed ID  9643345 Mgi Jnum  J:48030
Mgi Id  MGI:1261656 Citation  Semenkovich CF, et al. (1998) Effects of heterozygous lipoprotein lipase deficiency on diet-induced atherosclerosis in mice. J Lipid Res 39(6):1141-51
abstractText  Heterozygous lipoprotein lipase deficiency (LPL+/-) is common and has been implicated in premature atherosclerosis in epidemiologic studies. However, in vitro data suggest that LPL deficiency in the vascular wall may be antiatherogenic. To address the role of LPL in atherosclerosis, LPL+/- mice in the C57BL/6J background were fed an atherogenic diet for 8 months. LPL+/- mice were more dyslipidemic than +/+ animals due to increased concentrations of non-HDL lipoproteins. There was no difference in aortic origin atherosclerosis between LPL+/- (n=56) and +/+ (n=55) mice. LPL+/- mice in the low density lipoprotein receptor knockout (LDLR-/-) background were fed the same atherogenic diet for 3 months. LPL+/-LDLR-/- mice were more dyslipidemic than LPL+/ +LDLR-/- animals. There was no difference in atherosclerosis assayed for the entire aorta and no difference in aortic sterol content between LPL+/- LDLR-/- (n=28) and LPL+/+LDLR-/- (n=15) mice. LPL protein was detected in murine lesions in a consistent layered pattern. More luminal, lipid- laden macrophages generally did not stain for LPL, but deeper, lipid-poor macrophages as well as necrotic core regions contained immunoreactive LPL. LPL protein was more abundant in lesions from LPL+/+ LDLR-/- than LPL+/-LDLR-/- mice. After eating an atherogenic diet, LPL+/- as compared to LPL+/+ mice have more dyslipidemia, but no more atherosclerosis, and less LPL protein in atherosclerotic lesions. These data suggest that lipoprotein lipase deficiency in the vascular wall could prevent the retention of atherogenic lipoproteins.
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