出版社：American Society for Biochemistry and Molecular Biology
摘要：To elucidate the separate contributions of the lipolytic versus ligand-binding functions of hepatic lipase (HL) to lipoprotein metabolism and atherosclerosis, and to investigate the role of the low density lipoprotein receptor (LDLr) in these processes, we compared mice expressing catalytically active HL (HL-WT) with mice expressing inactive HL (HL-S145G) in a background lacking endogenous HL and the LDLr (LDLr-KO×HL-KO). HL-WT and HL-S145G reduced ( P 125I-apoB-intermediate density lipoprotein (IDL)/LDL (fractional catabolic rate in day−1: 6.07 ± 0.25, LDLr-KO×HL-WT; 4.76 ± 0.30, LDLr-KO×HL-S145G; 3.70 ± 0.13, LDLr-KO×HL-KO); HL-WT had a greater impact on the concentration, composition, particle size, and catabolism of apoB-containing lipoproteins (apoB-Lps) and HDL. Importantly, consistent with the changes in apoB-Lps, atherosclerosis in LDLr-KO×HL-KO mice fed a regular chow diet (RCD) was reduced by both HL-WT and HL-S145G (by 71% and 51% in cross-sectional analysis, and by 85% and 67% in en face analysis; P
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